If you already know what James Cameron has up his sleeve for the sequel(s) of Avatar, you might want to skip this post, because it's not about where he'll actually, eventually decide to go with the story, but about the constraints and choices he faces in making those decisions.
To begin with, you have a planet occupied by the Na'vi, who've had their moment of unmistakable first contact with an alien race, and won't be able to return to the innocence that preceded that moment. Moreover, as the first film ends, there's a small contingent of those aliens still on the planet, and most likely a few interstellar ships on the way at near lightspeed, with nowhere else to go other than to return to Earth, something they might not be able to do immediately or without resources from the planet. The Na'vi can cling to their nature-based ways, and their communion with Eywa, but they cannot forget that they are not alone in the cosmos, a fact about which they must surely be reminded each time their sun sets to reveal a sky half-lit by the gas giant about which their moon orbits, and the other moons which share it.
More importantly, the victory they've won is temporary. If RDA decided to take retribution, they could do it from the safety of space, by simply throwing rocks, which would arrive as meteorites, at Na'vi settlements and other strategic locations, beginning with their own base, to prevent news of the attack from getting back to Earth. To really defend themselves, the Na'vi would need a space fleet capable of intercepting and destroying incoming rocks or missiles before they reached target, and quickly. Perhaps Eywa could help with such a mobilization, particularly with accomplishing it without sacrificing their essential selves, embedded in the biology of Pandora as they are. Perhaps the tendrils with which they accomplish tsaheylu might be employed as a means of rapid instruction in science and technology. Perhaps a small percentage of the Na'vi might show an aptitude for such learning that would qualify them as geniuses on Earth, rapidly progressing beyond what they'd been taught to break new theoretical ground.
For Jake and Neytiri, there's the question of how much of Jake survives in the body to which his mind and soul transferred with Eywa's help, and whether he shares that body with echoes of his dead twin brother, the scientist, for whom the body was created and who presumably spent several hundred hours driving it before his untimely death, and before Jake. There's also the question of whether Jake can rise to the moment when doing so means making use of his celebrity to lead the Na'vi into a time of changes they cannot avoid, one which will continue long after his death.
There's a lot of sequel material there. How much of it translates well to a film the expectations for which are preconditioned by what was largely an action movie set on another planet remains an open question.