Mid-game is a loose term, as Fallout 2 doesn't have any chapters, or much preventing you from going anywhere right from the start. As a very rough estimate, it's about everything south of Redding and East of San Francisco.

Another consequence of the open-world of Fallout 2 is that it caters to many different playstyles, and not all of them will want to explore the midgame in the same order. In particular, some may want to "finish" an area completely, while others may prefer a much safer "come back later for this" aproach.

Each area will be cut into 3 sections : "pacifist", where quests don't involve any fighting at all (and thus the lowest risk), "normal" meaning what a typical canon adventure might be like, and "danger" for the challenging (at encountered level) bits.

Redding

Pacifist

The main highlight of the area is the large gambling den, right upon arrival. Slot machines have a limited payout (low hundreds per) but very low skill requirements, while the table on the left offers infinite gain potential, with steady benefits starting around 80 Gambling. A merchant with a lot of cash is also available. Cash is a commodity for the midgame, as several quests benefit from cash payments.

The sheriff has a bum leg and is looking for competent help (level 9+). The first few quests can be navigated with Speech only, but the last one (Morton) is a rough fight.

There's a fairly large, and fairly hidden, questline regarding Jet addiction, sprawling between Redding, Reno and Vault City (as well as the EPA for Restoration Project). Political ramifications extend even further than this, and will impact some of the endings.

Normal

Almost nothing here. The Morton brother can be fairly reliably taken out, however this is a fairly unnecessary risk. The guy is tough, has a gang with him, and more importantly his brothers will start ambushing you while world traveling, which can very easily end up in death-before-actionable.

Dangerous

The main story bit about Redding is the Wanamingo infestation, and it's quite unlikely that you'll be able to take it on until much later in the game.Doing so is possible, but require questionable tactic (zoning in/out) and an excessive amount of ammo.

New Reno

Possibly the largest city in terms of content, and likely in quality too. Appropriately located in the center of the map, many quests will have you come to or go from Reno. More so than anywhere else, you should explore diligently as unexpected finds and easter eggs abound.

On the other hand, the city is controlled by 4 crime families, none of which take kindly to insult or misplaced curiosity. Simply entering the wrong place might get you killed on sight, or at least cause the entire population to turn on you. If this is your first time around, save often.

Pacifist

Mob bosses

A lot to unpack here, much of which isn't of great significance. Setting aside the secondary flavor quests, you can chose to work for the 4 families and probably should. The questlines are mostly story-mode, and good ones at that. Becoming a made-man of a family however will not sit well with the others, so don't commit to one right away.

Each mob boss can be assassinated in a smart and sneaky way.

Mordinos : found in the casino in the first area. Lots of fetch quests. Little Jesus by the bar can teach you stuff about knife fight if he sees you armed with one. Old'man upstairs controls Jet production and distribution, and his weak heart couldn't take much drug use. Do you smell the poetic justice ?

Wright : recommended to do this as it is the only way to gain access to a huge army depot. Area is north-east from the boxing arena, very easy to miss. Daddy wants you to investigate his son's suicide. Ask a brother about him until he explicitely indicates which room was his, find an empty jet canister, interrogate street-level dealers, find out about poison, track it down to Renesco. You found the "killer". Pay the dude that welcomed you Reno for information about the families to understand the political mobile. Report.

The SAD outer grounds can be cleared without risk by sniping from cover. Once inside, expect very difficult skill checks, or quite difficult fights. Lots of loot. Don't report in unless you're ready to commit to the Wrights though.

His assassination path is iffy at best, and involves providing a loaded gun to the children playing outside.

Bishop : you need to have agreed to bring information from the heckler in Vault City (by the vault itself) for this to go well. Furthermore you must have been nice to him, or he'll have added a "kill the bearer" post-it. Unless you have a task to complete/report about, you can only be caught upstairs once until Bishop sets the guards on you. Both his daughter and his wife can be seduced without effort, but you'll have to go through his room on the way out, so plan ahead. Properly satisfying his wife can unlock a significant Speech boost, and is the way to assassinate Bishop through rewiring the trap on his safe. Do make sure do loot said safe to unlock the Raiders Base location.

Salvatore : very colorfoul characters. Hope you know your westerns. Possibly the first energy weapon you'll get

Car

Leave your car unattended in the first area and it'll be gone the next time you load in this area. You must track it down before leaving the area, or you'll never have a car again. If relying on the kid's tip, make sure you have a word with Jules or the kid will have an unfortunate skiing accident.

Once in the garage, head to the small office, and either pretend you're sent by the boss (free car, best option, hardest speech check), pay for the car yourself, or you'll have to fight your way. Diplomacy will let you get an upgrade for the car. Bluffing will also get you weekly free cells (medium & small).

Once the car has been secured once, it's safe to park in Reno.

Western area

The western area (with Renesco) has essentially no quest or story, yet is the most critical for hardcore playthroughs.

The shop has okay items, but asking about "special one of a kind items" lets you buy a voice modulator. The only other place you can get it is in Vault City, behind a skill check.

While the shopkeeper is tending the shop, lockpick the door on the far left of the building, then run in (dogs will bark & attract the owner, so don't dawdle) and down the stairs to meet "Boom" Algernon. Any gun that can be upgrade, he will upgrade for free. The upgraded version will also come with a full magazine. Scavenge the area to find rare tools, including an electronic lockpick. Try to leave during daytime to avoid the owner.

Normal

Essentially the "last quest" for each family falls here, as they all involve decently easy but essentially mandatory killings. Turning in any of them will generally preclude the others.

Once you gain access to the Stables (through Mordino's intro quest or a dealer's indication) you can meet Myron and start working on a solution to the Jet situation. He can be recruited or killed, but either will anger the guards.

Dangerous

Become the new boxing champion. No armor, no items. No working around it : you're one tough son-of-a-bitch, or you're dead.

Any of the crime family can be purged from the city. All the (matching) guards will aggro at once, and civilians will run wild. Many guards have full auto smg, and the potential to crit for <instant kill> damage, but other than that the only issue is that turns will take a while, and with so many to kill you'll need a lot of turns.

The stables can likewise be purged with holy gunfire.

Broken Hills

Too straightforward to mandate a walkthrough. Here are the cliffnotes, assuming you side with the mutants (as opposed to the racists).

Missing persons can be found downstairs, then north-east. There's a note on of of them, bring is back to Francis (optional) then report to Marcus.

Pacifist : possible but if you get surrounded by the ants, it's game over.

Play nice with the dude in jail, then tell on him to prevent a jailbreak.

You can test your strength in the bar, but unless you're on drugs, and don't mind spending the night as a mutant's toy if you lose (yes, for real), you don't really want to.

Mine's foreman will request your help fixing the mine. Renesco will get you the needed part, then you'll have to go in and install it. It's usually fine to just run in, but considering anti-rad treatments to be safe.

Pacifist : very difficult, mobs aren't neglectible and can surround you.

You'll need to find and help a mutant plant (bring a shovel) to best the scorpion challenge.

Lastly there's a very intricate treasure hunt questline, but so complex and obscure as to warrant looking up the in-depth walkthrough.

NCR

Before you do anything, pay the man 5$ to watch your car. Otherwise you'll lose it forever. Speaking of car, the bum on the far west can upgrade it for a few hundreds.

The shop near the entrance has 3 inventories (1 per shelf) and excellent items. Do not enter with guns drawn. In fact, this applies to the city itself too. And your companions.

Pacifist

East from where you enter you should be confronted (level-dependent) by a woman with a robot. To calm the man down, the pattern is 21212121... Anything else will blow it, although this does have benefits.

Best way for pacifists to get to Vault 13 is to track down a painting with a map on its back. Talk to the doc to learn about old man Saltbeef, grab a drink nearby. Talk to the sheriff about getting a job to be pointed to Westin, talk to the guard behind the electric thingy about said job to be let in. Give booze to Saltbeef, listen to his story. Head back to the doc and buy the painting. Voila.

Normal

The president wants you to negotiate with nearby raiders. Depending on how you decide to go about it, it's either "normal" or "dangerous", but either way it's straightforward.

If you decided to work for Biship, you can assassinate Westin quite easily.

Danger

Get rid of those filthy slavers, but don't do it until you've been offered the opportunity by the group in the garage for best results (especially with Restoration Project).

San Francisco

Pacifist

The man near the bunker entrance will task you with infiltrating the Enclave group. You need to accept the quest to have the option to infiltrate them (by pretending to be a new recruit).

Pacifist : if you're stupid (INT 3 or less) when you bring the plans back, he'll get the tanker in working order for you. Psycho gets you -3 INT per (-6 max) and mentats withdrawal -2 per (-4 max), stacking together. This is arguably the only way to reach the Enclave as a pacifist. For normal playthroughs though this is bordering on cheese.

Chip in the tanker has lost his spleen. He'll die in a few days if you don't help him. Track it down to the merchant left from SF entrance, then to the doc in the compound. Finally, pay the doc across the street from that merchant to put it back. Report to Chip.

Cal's (the "Gun" merchant in the tanker) sells most high-value chems in the game and restocks every 1-2 weeks. If you need anything (super stimpaks, psycho, mentats, ...) you can grind it out.

If you found the designs in Vault City, the doc here can set you up with combat implant surgeries. In the base game, those were quite glitchy and this is the safest doc to use.

Normal

The tanker needs gas. Many ways to fix that, and many glitches letting you fill it twice, or back and forth.

Dangerous

The cargo hold of the tanker is filled with mutated beasts & wanamingos. Very bad hombres. Don't mess with them without some of the best firepower the game has to offer, and even then you might have to fallback if they're about to surround you. The clean/canon way for the main quest is to clear a path there though, in order to access the left-side door and put in the navcom data needed to reach the Enclave platform.

Much like Reno, you can take part in a martial arts tournament.

Then...

A word on fighting

From here on out, you should expect to only ever be facing

Power-armored humans with the best guns of each category (Gauss guns, turboplasma, ...)
Mutants with high-end heavy weapons (gatling guns, rocket launchers, ...)
Tanky or high-damage beasts (deathclaws, wanamingos, ...)

You'll want to be able to survive a few hits from any of those (although a few crits can never be survived), and should have enough damage output to kill at least one such enemy per round, be it through massive number of shots fired, AoE, companions, or deadly aimed shots.

If you're using companions, many of them will just start being outscaled, in particular if they can't wear armor. Consider leaving them behind for now.

Clearing out the MIlitary Base west of SF should be fairly easy at this point. If it's not, you most likely won't be able to clear Navarro the violent way, so prepare accordingly. Either way, now is your best opportunity to take care of all unfinished business.

Tanker "go"

Your goal for the endgame is to get the tanker ready to go. For that you need

A FOB key from Navarro. Can be gotten without violence with a tricky speech check. Stealth may be an option, unverified.
The key will open a door (in the cargo hold, on the left) to the computer where you can install the NavCom part you found in Vault 13
Fuel. Easiest way is to ask Badger after helping any of his friend, although that may get him killed later.
Restoration project : to disable the submarine, or you'll explode when you "go". Just talk to the guy outside the tanker, many skill checks available and only one needs to pass.

Stupid characters likely won't be able to do any of those steps, but the game offers a dedicated solution for them (see San Francisco / pacifist).