I had tons of problems with the biology of the planet. I went to art school for god's sake, it's not like I'm a biologist.
If you look around the Earth, you'll sort of see continuity in animal physiology. Most reptiles, amphibians, birds and mammals share similarities. Bilateral symmetry, limbs follow a standard plan (one bone, two bones, many bones). And while not all of these animals have 4 limbs (snakes), most do.
For some reason on Pandora, every species has this biological USB port. So this is an adaptation of an extremely common...and therefore ancient, ancestor.
You have the blue lemurs, horses and dragons who all have 6 limbs. The Navi have four. The horses and dragons have 4 eyes, the Navi and Lemurs have 2. The Navi appear to be from a feline line of decent, but the only other creature which appeared to be from that family also has 6 limbs and 4 eyes.
I mean, everything on this planet has 6 limbs, except the Navi and they don't even have vestigial nubs where those limbs used to be. My first instinct was "Oooh, it'll turn out that the Navi are alien to the planet", but that wouldn't make sense either since they have the unique and ancient USB adaptation.
Humans are a 98% genetic match with a handful of species on this planet. The percent drops incredibly by the time you get to something that has a totally different number of limbs than we do. You're talking 340 million years to when proto-mammals and proto-reptiles branched, and it's not like snakes DON'T have 4 limbs, they've just evolved not to need them. They still have vestigial bones.
The Navi appear to be the most well adapted species (tool making, they're in the forrest, plains, mountains...they're everywhere) on the planet and appear to have no genetic relatives. It's as if the genetic branch for 4 limbs, 2 eyes is extremely successful...except for every other species on that branch died out in favor of 6 limbs 4 eyes. It's a contradiction.
Yeah, this is really really really nerdy... but again, I'm an uneducated whelp.
TL:DR; When one is spending $500,000,000... kick $20,000 to a scientist and say "Hey... does this stuff make ANY sense?".