I'm looking for something that will allow multiple styles of play. Something that can handle gritty and nasty to uber over-the-top action. I would also like something that allows tactical combat with miniatures but does not require you to use them if you don't want to, or the combat is small enough to handle without them.
I think alignments should be optional, I've never liked the D&D system all that much.
Combat should be faster and a bit more deadly.
Powers, as they are in 4e should be optional, and if included should probably be feats.
Though I know it will never happen, I hope they drop the static defenses in favor of a defensive action, like parry or dodge. Would go a long way toward improving melee combat IMHO.