Well, South America is generally represented by the Incas and that is because it was the largest empire and probably the most advanced in all of pre-Columbian America. In just over 100 years, the Incas managed to defeat all the kingdoms and peoples they faced (well, except for the Jíbaros, but that’s probably because they used the Amazon jungle to their advantage).
Personally, I would love for the Jíbaros to be a playable civilization because they have had worldwide influence in various media, such in the Blizzard games (which are also part of my childhood and adolescence) and I learned about the history of the peoples Amazonians when I worked a season in the Amazon rainforest and many of those stories are worthy of legends.
Another interesting South American civilization is the Guaraní who supposedly stopped the Chanka expansion (before the Chanka-Inca war) and tried to invade the Tawantisuyo on more than one occasion.
The Muiscas/Chibchas would be an interesting civilization, they could appear as a allied civilization in the battle of Cartagena de las Indias
Edit:
It would also be interesting to explore the concept of miscegenation in America, and concepts such as “the colonial Inca nobility”
