From what I've seen of previews and hands on with several games like God of War, GT5 and Heavy Rain and the early/Japanese reviews of FFXIII, I don't see what could beat it, though the early release could hurt it some.
My fingers are crossed for Halo: Reach being mind-blowing, but an FPS would have to iterate a WHOLE lot to top Mass Effect 2. Possibly Bioshock 2 or Fallout:New Vegas or Fable III based on the reception of previous installments?
I think Mass Effect 2 is fairly brilliant in terms of story-telling and engagement level.
But who knows? Maybe one of our new IP's will come out of nowhere and blow us away. That would be so great for gaming.