Re: Resident Evil 6
No, not at all. It's not a canonical game, though. The only ones you need to worry about are the numbered games and Code Veronica (which comes between 3 and 4.) Again, the remake of the first is recommended over the original. Though the original does have some unintentionally hilarious dialogue.
"In Brightest Day, in Blackest Night, no evil shall escape my sight. Let those who worship evil's might, beware my power: Green Lantern's light!"