Thief: The Dark Project - was utterly unique when it came out, and still has features I've yet to see in any other game. AI alone do things I never see in other games.
Bulletstorm - It is the first shooter I've played seemingly designed from the ground up around performing combos. A unique kick and whip that slow-mo suspend characters to make it possible to perform them, with a large suite of unique multi-function weapons, enemies with positional damage that tracks crotch shots, and an array of alien environment hazards. Also one of the only FPSs with a not-terrible boss fight.
Super Time Force - unique take on time manipulation to essentially stack ghost runs of your previously controller side-scrolling shooter guys. It requires I think differently to win vs. any other shooter I've ever played.
SUPERHOT - another shooter that makes me think completely differently, with a world that moves only as you do, and has this amazing flow that is among the best hybrid I've ever seen between turn-based and real-time.
Homeworld - the first RTS I've ever seen take real advantage of 3d space, with a unique campaign structure that features a moving through space mothership producing units, and resources + units carry over to the following missions. It's a different experience from anything else in its genre.
Deus Ex - A unique Action/RPG that prioritized player choice/agency to a such a degree most games still don't get close to. Stealth, hacking, combat, conversation, a wide range of abilities in non-linear levels just provide this amazing diversity of play that truly can be a different experience multiple playthroughs.
XCOM - It takes a premise of alien invasion, and builds a strategy game around unique aspects of that premise. Harvesting aliens to gain attributes of their technology, persistent troops that can die without the game ending, responding to crisis around the world, dealing with your own base getting invaded, and tactical combat that allows for an excessive amount of dynamism.
Magicka - Pretty simple, because it created a system where you craft an incredible myriad of spells from elements on the fly. I've seen nothing else like it.
Gunpoint - Unique approach to infiltration through re-wiring the level you're in.
Invisible Inc. - Another utterly unique cyberpunk turn-based stealth game where you have few to often no lethal tools at your disposal, can leave a mission failing it without the game ending, sit on top of guys pinning them in a knocked out state, and exploration utterly essential to gameplay.
Transistor - unique hybrid of turn-based and real-time combat, that can be played full in one or the other depending on how you spec a character. The way you can slot abilities around to stack effects is something I haven't quite seen in anything else yet.
F.E.A.R. - horror FPS hybrid with a unique mix of slow-mo essential to deal with AI design I had never seen before on release, and hasn't been done better imo since.
Smash Bros. - A unique take on a fighting game with platform elements, a unique health and ring-out system, and unlike other fighting games incredibly easy to pick up.
Others:
- Audiosurf
- Brutal Legend
- Chime
- Company of Heroes
- Crysis
- Don't Starve
- Door Kickers
- Brothers: A Tale of Two Sons
- The Banner Saga
- Far Cry 2
- FTL
- Guild Wars
- Grandia
- Just Cause 2
- King's Field
- Massive Chalice
- Mario Galaxy
- Mario Kart
- Monaco
- Offworld Trading Company
- Papers, Please
- Planetary Annhilation
- Power Stone
- Psychonauts
- Reus
- Sang-Froid - Tales of Werewolves
- Rogue Legacy
- Titanfall
- Tribes
- Trine
- Tropico
- Unreal Tournament
- Valkyria Chronicles
