Borderlands 2. No contest. Basically Borderlands 1, which I love, but with a lot of the obvious wrinkles, like brown art design and bad PC porting, ironed out. And I know that applying the Diablo formula of watching numbers tick slowly upwards is a very love-or-hate thing, but I happen to love Borderlands and I'm really hoping Borderlands 2 is a success.
Looking with somewhat less interest, but still some, at:
-Dishonored; published by Bethesda (so it'll probably have more bugs than most), but made almost independently - then again, so was Brink, and Dishonored is promising almost as much as Mass Effect 3 did
-Far Cry 3; made by Ubisoft, so it's likely to have DRM bogging down the PC version - then again, I didn't mind Uplay for Assassin's Creed 2 (in 2012, anyway) and between Rayman Origins and the stuff they put on GoG recently...
-Bioshock Infinite; which seems to take a better approach to 'sequel' than Bioshock 2 did, but I've heard that Booker DeWitt has a lot fewer pockets than Jack did (i.e. two weapon slots) and that made me a bit more dubious. Also, it doesn't come out for a while compared to the others.