Avatar 2 and Avatar 3
Because of Cameron's statement, specifically that he expects "that those nasty humans didn't just go away forever [and say], 'well, that didn't work,'" I'm dreading that Avatar 2 will be too much of the same. But I also thought of how it seems like Empire Strikes Back and could be more of a bad guys win angle. For that, though, we'd definitely need to explore completely new settings on Pandora, just as the Star Wars sequel brought us to fresh environments like Hoth and Dagobah. We did see a few other kinds of terrains during a montage in Avatar, so perhaps the sequel can take us to one or more of those. Or something we haven't yet seen.
As for specific story arcs, what can Cameron do? Unfortunately, he doesn't have a Delgo sequel to look to (just kidding). So let's think of what he's done with sequels in the past. Both Aliens and Terminator 2: Judgment Day improved, at least in size and scope, from their predecessors. If Cameron was going to go his Aliens route, he might increase the quantity and threat of the enemy. But who wants more marines? Instead, maybe the nasty humans could find some nasty alien race, maybe from another planet, to assist as a powerful ally?
As for the T2 route, in addition to developing a more deadly enemy, Avatar 2 could maybe play with the idea of seemingly swapped allegiance. Like Arnold Schwarzenegger's switch to being a good guy in the Terminator sequel, maybe Sam Worthington becomes a villain in the Avatar sequel. Or least an ultimately apparent villain, like a pseudo double-spy. Basically, the real Jake is lost or trapped somewhere while another marine (or android) -- or maybe Jake's twin turns out to be alive -- is disguised as Jake's Avatar. It's like the original plot, but twisted back on itself. It's also potentially a bit too much like a billion other stories, including Face/Off, Bill & Ted's Bogus Journey and TV's Lost.
What else is there? Cameron's upcoming prequel novel will apparently deal more with "feelings" and what the characters are thinking rather than concentrating on back story adventures and such. Maybe you'd prefer Cameron focus more on adding to the dimensions of his characters in this way rather than figuring out how to go bigger and better with plot and effects?