I would hope it's any game but GTA4. Gta4 stripped everything that the series evolved into for "Next Gen" graphics. No planes, stat building, turf wars, multiple business's and property to buy, extensive amount of weapons, and to top it all off it just is a hypocritical story about a man seeking redemption yet kills indiscriminately to further his tragic past. I've played it all the way when I first bought it to the redemption choices for the ending then put it away since about a month ago. I finally beat it just cause I haven't and was underwhelmed by the easy and kinda lame last mission. GTA4 wasn't a bad game but coming from the evolutions of vice city and san andreas a TRUE GTA fan would be very disappointed.

I mean Brawl added a lot to melee, MGS4 changed the whole series, Fallout is taking a brand new direction, LBP is well...unique.

The longshots seem to be GeoW2 and Resistance 2 and I just don't see them doing anything that much different than their first iterations.

okay, GameSpot gives 10 nominees so here's my two cents:
? at the end means maybe, otherwise it's definitely

In order of most-least likely to win

MGS4

GTA4

LittleBigPlanet

Gears of War 2

Resistance 2

SSB Brawl

Burnout Paradise

Braid (for some reason)

And two of the following: (in no order)
Sins of a Solar Empire? (they have to put SOME PC games in)
Fallout 3?
NHL 09?
Civilization Revolution?

I think MGS4 can take GoTY (it even says so in my sig)

That is unless they succumb to the hype of GTA4. I would be really annoyed if that game won.

I'm pretty sure IGN will say MGS4 because they said if they could they would give it an 11/10.

Mega Man 9?