I've got some oldies:
Anachronox - released in 2001, it's the newest one of the bunch. A TPP, JRPG-style game using a modified Quake II engine. Graphics might look clunky by modern standards(less so than System Shock 2 though), but the game has fun writing, good voice-acting, inventive locations and a goofy kind of humour.
Albion - a mixture of SF and fantasy, you are a part of an outworld mining copany expedition sent to a new mining site that was supposed to be uninhabited but obviously isn't.
The gameplay is party-based, and split between two modes of exploration: top down and FPP, with grid-based combat.
I simply love the atmosphere in this game, there's something about the art direction that made it feel unique. Might be just my nostalgia speaking though.
Superhero League of Hoboken - it's a post-apoc game, but with a twist. You are Crimson Tape and you have the power to Create Organizational Charts. There's others too, with similarly useful powers, that join you on the mission of fighting for the better tomorrow. Or something.
Gameplay is a mixture of adventure-style problem solving and RPG combat/party management.
Lots of low-brow, but witty, humour.
BloodNet - a cyberpunk vampire story, with varied gameplay(there's an epilepsy-inducing net-surfing part for example) and tactical combat.
Megatraveller 2 - a huge game, in the Daggerfall sense: lots of locations that all look very much the same. Still, there's ground and space combat(the former being something I could never understand), a universe-saving story, and a character generator that is the most fun part of the game. The generator was obviously made to supplement the tabletop RPG system, and lots of results/stats are never used in the computer game, but it's still a ridiculous amount of fun to play with it(it's that career-following kind of generator).
Perihelion: the Prophecy - hailing from the glory days of Amiga, this 32 colour-palette game is an RPG for hardcore fans of the oldschool, and nostalgia-ridden old geezers. Gameplay looks like that of Dungeon Master, albeit with tactical, action points-based combat.
You are a team of genetically-modified hybrids sent to stop what is basically an antichrist.
Quite frankly, the game is not too stellar, but has an unique feel to it that warrants at least a passing acquaintance.
edit: dungeon master, not keeper