Core War - Not for the feint of heart; a programming game, extremely difficult to learn.
Dragon Age: Origins (see also Awakening) - Western RPG, quite epic at that.
Dungeon Keeper 2 - Unique RTS. Build and manage an underground dungeon; fight.
Heroes of Might and Magic 3 - Unique turn-based strategy. Difficult to describe.
Jagged Alliance: Deadly Games - A very old but good turn-based tactics game. Hire then manage a squad of mercenaries on missions.
Katawa Shoujo - Interactive audiovisual novel. Possibly the most emotional game you'll play in your entire life.
Moonbase Commander - Unique turn-based strategy. All base-building; you fight directly with your base.
Gunman Chronicles - Lesser-known cousin of Half-Life. Same engine, came out the same time. Almost as good.
Master of Orion 2 - 4X game unlike any other. Manage a space empire and design ships in unprecedented detail. (do not play Master of Orion 3)
Saints Row 2 - Grand Theft Auto but fun. Massive performance issues on the PC port... and even then, it's still a must-play.
Wario Land 2 - Old Game Boy platformer, but very interesting in its design. You can't die, so the consequence for failure is novel.
Dominion - Unique card game. Build your deck as you play. Every game is different. (
play online, free)
Advance Wars (series) - Turn-based tactics. Best part is in the atmosphere, but gameplay is solid as well.
Donkey Kong Country (series, see also 2 and 3) - One of the best platformers ever made, the whole series.