It looks like Nintendo is gonna working on something major for the Wii game. IGN says that GameStop was told to keep some shelf space open. I'm not sure of the last time game makers requested stores to reserve shelf space but it sounds like something monster.
I think the game will be from from one of three franchises in particular: Star Fox, Earthbound, or Kid Icarus. There hasn't been much of a Star Fox blockbuster since the one on Nintendo 64, but the characters could still be seen in Super Smash Bros. and the occasional sequel. There has only been one Kid Icarus game and it would be nice to see a comeback title. EarthBound is the only MOTHER game to reach the US (Japan has seen quite a few). Maybe that will change with this new game.
We will probably find out at E3. Until then, your guess is as good as mine.