I think it would be the easiest for Microsoft to lose actually. If they announce the 720 as less of a gaming device and more of a media hub, while focusing on Kinect2, dragging out the conference, and showing very few games....it could very well be disastrous. I'm not saying that will happen.....but it is one of several scenarios that could happen.
Sony will be talking about the hardware, price, how the sharing stuff will work a bit more, and showing off game demos.....I expect Knack, Killzone, Driveclub and Infamous to feature heavily, and maybe Destiny as well unless Activision showcases it at their event instead. Hopefully they will have some surprises for us in the way of launch/launch window titles instead of relying on 4 or 5 games to carry and sell the system. For me, they almost have to announce The Last Guardian for me to pick up a PS4 at launch. I plan to get one, just not until there are games that interest me.
Nintendo has been doing a little house cleaning lately. With today's 3DS blowout on the Direct and an all-day event in NYC (I think it was today, for hands on demos of some of the things shown), it seems they are clearing E3 space for Wii U. Sure they will touch on the 3DS and how it is kicking butt at the moment, but they are going to blow the doors off the place with Wii U stuff. WWHD, Mario (Luigi?), Mario Kart, Yoshi (seems likely) Bayonetta (first full trailer), Smash Bros (first trailer), "Efforts from [our] 3rd party publishers on Wii U" (Iwata quote from the January ND), other surprises?, and most importantly....whatever the hell Retro is working on (supposedly it is gorgeous and 60fps).
Unless one of them REALLY messes up; Microsoft being dumb, Sony not telling a price or having 3 games at launch/boring us to death a la Wonderbook, Nintendo focusing on 3DS for some unknown reason....each will have people saying that their favorite company "Won" E3. One thing is for sure though, it is going to be an amazing event. I'm not making any sort of prediction as to who will "win"...seeing as it doesn't really matter, just like whoever "wins" the console war.
You know who really wins? Gamers.