I'll be honest, despite sacrificing some key elements of the series that RE4 managed to keep, I actually had fun with RE5's gameplay. Its story on the other hand, was total crap. It started like a spinoff but spiraled into something of a supposed conclusion for the series. I have no huge gripe with Sheva, but she sure as hell didn't deserve to be the one to make Wesker eat that rocket. It would have been a lot better if Wesker weren't involved at all.
They have plenty of places to take the story; Tricell has the G-virus after the CGI movie (though that's getting a sequel, so more stuff could happen), and just about every other B.O.W. and virus in the series is on the black market. The series needs to go back to its roots, while keeping the best innovations intact.
Hell, imagine running through an abandoned street, only to bump into a crowd of slow zombies numbering in the dozens. You have nothing but a pistol, with nowhere near enough ammo to kill them all. Your options to A) run from them and go into the nearby building or B) get surrounded/cornered while trying to play Rambo and get eaten alive. I want situations you can't beat with the prowrestling crap in the past two games. You can get away with that with Las Plagas, but I sure as hell don't want my arms to get eaten.