Personally for me its going to be Saints Row 3. I dont give a flying fuck about about Skyrim. didnt care for Oblivion either. Deus Ex is a bit meh personally given the move backwards to "Lets make it a Male only Protagonist" after Deus Ex 2 had the option of being either gender, though it still has a chance to win, given the series being as successful as it was, but that may be a DNF Moment, i.e. the "old nerds" expecting the second coming from nostalgia. So it may turn out bad too, Deus Ex that is :3
Other contenders for it would have been ME3 for one, but thats pushed off. Portal 2 prolly wont win it, while the game is fun and interesting, the Idea isnt new anymore and having just the humor and fun but short gameplay may not save it a top spot. Everything else so far has too little concrete Info to judge, at least in my Opinion. But in any case, its really that any game could win, as long as the Game turns out to be awesome.