Well it won't be Nintendo. So scratch them off.
Between Sony and Microsoft. Tough to say. I'm not sure what a megaton from Microsoft would be. While we might see some huge game announcement from Rockstar at Microsoft's conference that will inevitably be on the PS4 as well. More Halo wouldn't exactly be a huge announcement.
Where Microsoft could do something big is unveil a more powerful and redesigned Xbox One. That would be, if Sony doesn't unveil a PS4.5, the biggest announcement of the show.
I'm not sure if Sony can pull off a Year of Dreams 2.0. What would be a huge announcement would be is if they announce a new Crash Bandicoot and Rockstar resurrects Agent.
I think Microsoft needs to kill it. They're in this funky spot where I think they're unsure of what the future of Xbox is. They're in this weird middle ground where they're not in dire straits like Nintendo nor are they enjoying anywhere close to the success Sony is. If VR blows up then they've missed the boat on that. It's been long enough now where we should really be seeing the fruits of Microsoft's restructuring post Mattrick.
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I really hope Microsoft has a mic dropper. As a gamer, I'm rooting for all these guys doing well this E3 (: