I signed up to reply to this thread so, here goes:
My guess for the "big unknown title" is a free-roaming Pokemon. I think that any online functionality will be relegated to Arena style matches with the pokemon you found and trained in the single-player portion. Trading etc will also be possible but I doubt that we will get a MMO. I imagine a game as a crossover between Twilight princess, Oblivion and traditional pokemon games off course.
It also fits the description best. All casual gamers know of pokemon (even more so then star fox, Donke Kong etc - titles I'd also love to see) and line up to play it. And us, the definite hardcore crowd would immidiatly buy it. I know I would. And I tink that you guys would love to see a fully rendered 3d world where you can freely pick and choose where to go - apart from off course the regular stuff where you have to solve a puzzle to continue on a path...
My bets for an announcement on E3 '08 would thus be:
Animal crossing ('08), Zelda on holiday 09, Star Fox somewhere in end Q1/Q2 09, and pokemon RPG as the big secret reveal of holiday 08.
The Doctor will see you now
Promoting Lesbianism --> 
