I voted for Aztec/Mayan. With 'Aztec' included in the title of this setting we already focus on a fairly short part of the precolumbian Mesoamerican past (1325-1521 AD). This is a good thing, mind you, because it's no use trying to filter a usable game setting from thousands of years of history. It would be most interesting to present a detailed image of Mesoamerica during the reign of the Aztec Triple Alliance.
There have been a few products on the RPG market concerning Mesoamerica but unfortunately most were not done very well, and that's keeping it friendly;). In fact I can think of only two decent products: Steve Jackson Games' GURPS Aztec and Pagan Publishing's CoC sourcebook Mysteries of Mesoamerica, though the latter is of no use for setting your game in the precolumbian past because it lacks decent, recent and clear information on the period. So we're basically stuck with one source, which is a bit meagre.
Regards,
a Mesoamerica fan