Well, let's look - what are Nintendo's major franchises left? I'm only considering the "big hits" which is 5M +
Mario Party 9 could make 5M.
Another M&S
Another Zelda
Another Mario Platformer
A Pokemon console title (it's possible).
Donkey Kong (doubtable, and even if there was one - would it sell 5M?)
Starfox (would it make 5M? I kind of doubt it, but it's possible).
So that's the major titles they have from the last 2 generations (5th + 6th). None of those will beat 10M though (M&S combined has a shot... Possibly the Mario Platformer).
So other than that, it would have to be a new IP, a revival of an old series (pre 3D, so it would really be the same as a new IP) or a handheld transformed to Wii game (which would also need total remaking)
That means these are all the titles that we can expect to be released that will make 5M. Oh, that is, of course, excluding any Wii series game.
What's likely to be first?
I have to say it seems pretty obvious... Mario & Sonic or Mario Party.
Then we have to as ourselves; third party?
Yes, can any 3rd party title make 5M (or more)? I doubt it, but it is possible. A Guitar Hero has a shot.
So my answer is: Mario Party 9. We know it will come eventually, and M&S isn't even announced. MP9 is simply the one of these titles I believe will be released first.