If you want something as a radical change of pace and strategy for a game, try Postal 2's harder difficulties. The POSTAL difficulty, for example, makes everyone shoot you on sight, you cannot store health items and you can only save once per area. However, because everyone drops ammunition and armor, you're actually a bit incentivized to be as aggressive as possible and shoot any person you see before they can open fire, kinda like in original Postal. Nice and psychotic. You can try speedrunning and pacifist runs as well, as many of the game's tasks can be skipped by just either having enough money or waiting a bit.
The crown jewel of the game's challenge runs, however, is the Ludicrous difficulty. The ruleset is as follows:
> healing items only heal you on picking up with the exception of crack, you can store only one pipe which will heal you for 30 HP but will hurt you for 75 HP later on
> only save once per level with the exception of autosaves and checkpoints
> every rule that allows the NPCs to get dismembered also applies to you, if you eat a machete you'll die instantly
> weapons don't drop from enemies, only a bit of ammo does so you have to find them yourself
> every NPC has access to endgame weapons like mininuke launchers, which will promptly obliterate half the map and you if you don't hide
> NPCs do not run away and will actively run into you if set on fire
With all that included, the game becomes a real test of everything you know about it. Rob a bank on the first day and get the money to buy as much pistol ammo as possible and storm the Al-Qaeda secret base just to get a machete that makes melee kills easier, land faraway rocket launcher hits just to not interact with most of the level, fear open spaces and streets like fire, use gasoline as area denial, learn that weapons actually have their niches you never considered, learn the map and the location of every item by heart because you WILL need all of it. Most ass-shattering 6 hours of my life.