If I go by the amount of time invested, I gotta say
1) Borderlands -I played the shit out of this game. Even if the quests are so samey, I just can't stop shootin' folks.
2) Everything else.
Seriously, though..
2)Pinball FX2 -Don't judge me. I love real pinball and since real tables are rare as diamonds these days, I gotta play this. Doesn't hurt it's a really good pinball game with lots of tables and new tables all the time.
3) Red Dead Redemption- Such a giant, open world time waster, I've never actually finished the game in all this time. I'll ride around for hours just to find the best place to watch the sun rise.
2)Bioshock - Dark, drippy and one of the only FPS games I really liked. (Borderlands doesn't really count. The shooting in the game is secondary to the looting.) The Fort Frolic segment with Sander Cohen is one of my favorite game experiences ever.
1)Diablo 3 - Screw the haters, I like this game. Hitting a demon so hard with an axe his skeleton pops out is satisfying on a primal level. And I love looting. Finding shit in boxes and off of corpses is something that pings in my brain, so Diablo games do it for me.
There's plenty of runner's up - Bayonetta, inFamous, UMvC3, Dead Rising 2, AssCreed 2. This has been one long-ass generation of games.