Additionally, unlike much of North America, Central America and South America had true political empires. The Aztecs are already in-game, and were the most obvious pick for Central America - though that region had other realistic candidates such as the Maya. South America, on the other hand, only has one realistic candidate - and it is now the only region in the America's to have no indigenous representation. Add to that the (arguable) fact that the Inca were the most technologically and politically sophisticated empire that we are aware of to have lived in any of the Americas... it is really hard to imagine them to not be included.
Even still, it is possible that we may get a curve-ball (especially given the seeming interest in including more civs that haven't been represented before, as well as being more diverse, on the part of the developers). If that is the case, South America could end up with Gran Colombia or even Bolivia (Simon Bolivar has been an interesting omission over the course of the series) as a civilization - and I'd have fewer reservations about than, say, Canada as there is a stronger claim to indigenous political power in the South American post-colonial states.
Also, if there is somehow another European civilization (if you don't consider Georgia to be European)... has anyone discussed the possibility that it isn't Italy but rather the Holy Roman Empire? The Holy Roman Empire fits R&F better than the Italian city-states and it could also be used to include some of those city-states and even the Vatican, depending on how liberal they are with city names. The Holy Roman Empire would be perfect for alliance and loyalty based mechanics.