The point of 300 was that it was a heroic, doomed battle that caused far reaching, positive effects. Like "Charge Of The Light Brigade" but meaning more in the big picture.
Given that pretty much everyone dies in 300 and it's about that one event, I can't quite see how a sequel is really possible. Sure you could do another battle around the same time period involving the Persians, but honestly it wouldn't truely be a sequel. Just another Greco-Roman muscle movie.
I suppose they could reverse the roles to some extent, have The Spartans become the bad guys, and do the war between Athens and Sparta in a really cinematic fashion.
If Brad Pitt wasn't apparently so busy, I could see him making a return to the gladiator-flick genere. He did okay as Achilles and could play that kind of character again.