I'm definitely pumped for the highly advertised showdown between Chris and Wesker in this entry of the series.  Does anyone think that this is going to be the end of our favorite reflective-shaded antagonist, or wil he live to see Resident Evil 6?  There's certainly a lot of evidence pointing in that direction (some of the dialogue from Umbrella Chronicles comes to mind), but I don't think he will.  Capcom is finally beginning to play him up as the mastermind conspirator behind everything, and so I believe that Wesker will prevail at least this once more.

I think, for the fans of the series, Wesker stands as the most iconic villain in the games' collective narrative.  Without him, there is a serious gap in tonal continuity.  I mean, take Resident Evil 4.  Sure, it was a good game, but not until Wesker's appearance on Ada's PDA did it feel like a real entry in the Resident Evil series. 

It's sorta like taking Bowser out of Mario, because Wesker is still the figurehead for Umbrella.