Being that it has been shown (in some form or another) at two previous E3s I don't think that it can have as much of an impact as you would think ... Now, I'm not expecting Zelda but being that the last Zelda was released late in 2006 (with most development being completed well before that) so the next Legend of Zelda game could already have seen 18 to 24 months of development by now.
The "Biggest" game of E3 will probably depend on who you ask though ... The core gamers for the PS3, XBox 360 and Wii will (likely) each have their own answer which will be drastically different from what the more mainstream gamer (and mainstream media predict).
The game I expect to be huge and receive no attention because it is not on a home console is Dragon Quest IX.
