To early to tell.
My projection? Toss up between Mass Effect 3 and Skyrim.
Mass Effect is, I think, the less likely of the two, seeing as the second lost in a lot of contests to Red Dead Redemption. In fact I think IGN was the only one I can think of that gave ME2 GOTY. Still, the third installment is getting a lot of hype, and there's a good chance BioWare will be able to refine the things that worked enough to grab the trophy.
On the other hand... Skyrim. I mean, just Skyrim. Every game Howard's team over at Bethesda Game Studios has made since Morrowind has been Game of the Year. That's a damn good track record. Then there's development time to think about. ME3 only had a 2 yr development, assuming they started it 6 months before ME2 was released. Skyrim has been in development since Oblivion was released (2006), though it didn't get the team's full attention until Fallout 3 was released (2008). That's still a full year longer than ME3.
Oh, and btw: None of the games from the past couple years that bear the Bethseda Softworks logo were actually made by Bethseda Game Studios. The two are not the same thing. Softworks is the company's publishing arm. They do a lot of third-party publishing (often on really crappy titles like Wet and Rogue Warrior).
Bethesa Game Studios is the company most people think of when they hear Bethesda. The only games they've made in the past decade are Morrowind, Oblivion, and Fallout.
Just figured I'd throw that out there since a lot of people tend to incorrectly attribute some games to BGS.