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Slimebeast said:

I mean biggest as in many factors combined (not just sales but also review scores, number of GOTY awards, hype, fanbase, media attention and stuff like that) but it's probably too hard to define and agree upon.

So by my definition it will clearly be "bigger" than Uncharted 3 and Mass Effect 3 but to compare Skyrim with Call of Duty 2011 and decide which is bigger will be hard.

It'd be hard for Skyrim to be "bigger" than Call of Duty at all, since CoD will probably sell about three or four times as much, but I understand what you mean.