MGS4 - this game is sooo amazing, right up there with Subsistence for best in the series, maybe better (way better gameplay, deeper, but MGS3 always score points for its plot & setting).
Oblivion - disclaimer, I still haven't played Skyrim so that may well unseat this, but I'm a big Elder Scrolls fan and put a ton of hours into this.
Valkyria Chronicles - Arguably the best JRPG of the decade, imo. Memorable characters, music, an incredible art style, deep customization, cool plot & setting, and most importantly the mechanics are fun as hell, something you can rarely honestly say about JRPGs. Beyond underrated.
Still a lot of games I haven't played yet this gen though. This list could look very different 18 months from now once I've finished Deus Ex HR, Xenoblade, all the MassEffects, Skyrim, all the Uncharteds, Tag Tournament 2, Halo 4, etc.
Honourable mentions to Wipeout HD, Metroid Prime 3, Alien Crush Returns (don't laugh, put so many hours into that on Wii), Tekken 6, Super SF IV, Ridge Racer 7.