I remember that last E3 nintendo had something to show us from Retro Studios, however the unveiling was cancelled at the last minute (or so I think that's what happened). So the game they're working on has to be well along by now, but nintendo being nintendo, we won't hear anything of it until 6 months or so prior; which is what I love about nintendo :D . Hopefully we'll hear something about the new retro game at this E3.

new IP im betting

Metroid Prime Hunters 2?

Since I still think Kirby might still be release this year (hopefully), and
Star Fox and F-Zero might have be developed by Nintendo themselves (due to the last games are a "disappointment" for Nintendo according to Wiki)...

And, since I believe Retro Studios is exactly that - "Retro"
They are working on classic IP who are in need of a comeback:

-Kid Icarus (which is also my guess)
-Donkey Kong, or maybe
-Earthbound

Kirby Parade!

It's basically Wii Music, but it involves Kirby, so it'll sell 10 million guaranteed.

Metroid for Wii 2 anyone?

F-Zero: Captain Falcon's Adventure. It would kind of play like Yakuza, but instead of fighting in the streets you RACE! Rawr!

'Twould be badass.

i don't see this happening. I thin with other M they are moving away from the Prime series. Plus I think Retro is needed for console development far more than handheld development, if they want a MPH2 they'll just give it to NST again

Probably a new IP. Nintendo is needing some freshness in their catalogue right now.