I see E3 being split into multiple Directs simply because there's so much content they could be showing. I imagine there being maybe 3-5 Directs? Possibly plus Smash...
Dependant on how many Directs there are I could see one Smash reveal per Direct being the norm.
Highly Likely (66%+)
Nintendo Direct @ E3: Teasing various upcoming releases, maybe giving release dates for stuff like Zelda Muso, showing off the upcoming 3D Mario, Zelda, Retro's Metroid, No More Heroe 3 etc. [Mewtwo/Pac-Man probably for optimal hype induction]
X Direct: It's a big one and we've barely seen anything at this stage, but it is a very big game... they've got to do a big Direct on it at some point though, and E3 is the time to get the hype out of it. [Shulk Reveal]
Dragon Quest Direct: The amount of motion going on at Square Enix is palpiable, and I'm sure, given that Monsters, Slime Mori Mori 3, DQVII and X are all on Nintendo consoles... and Yuji Horii has stated that DQXI will be on a Console (this basically means Nintendo too given that's where it sells best)... I'm pretty sure Nintendo will grant them a Direct to show off what's to come for both the west and Japan. [Slime, obviously.. assuming he's in..]
Somewhat Likely (33-66%):
Zelda Muso Direct: I imagine there's a lot to talk about, it really depends on how soon it's coming out if they'll get the Direct or not. [Reworked Ganondorf? Girahim?]
Bayonetta 2 Direct: It's a major 3rd party release, I really don't think Bayonetta's getting into Smash, but if she is, this could be where she gets shown off...
Smash Direct: They left things to be discussed later, but it is a bit close to the last one... [could be anyone]
Farily Unlikely:
Metroid Direct: Being a western focused series E3 is the place to hype it up, and we know Retro have been working on it (or atleast something, but I'm pretty sure it's Metroid given Reggie's Pin incident) for at least a while... I just don't think it's going to be ready for more than a teaser by this point... if it is though... [Ridley, obviously]
Indie Direct: Nintendo are pushing the Indie front, and with stuff like A Hat in Time, Knite and the Ghost Lights, Churbles, Azure Striker Gunvolt... and all the Unity games they've not mentioned yet there's more than enough for a Direct about it... again, not expecting a Character out of this one.
Very Unlikely... but:
Rare Direct: If Rare have changed hands they're getting a Direct at E3, and possibly/probably a Banjo reveal... but I do not expect Rare to have changed hands...