Im doing a colonization remake and I'm working with what native tribes to include. The focus is less on US and more on the Caribbean and plantage economy than the original. See my suggestion in the image.

What about Yutucan peninsula? I know the Mayan empire is long gone in the year 1600 but there is still Mayan city-states of some significance. I could just have "nothing" there but it's a bit boring.

The amount of native players (ten) is fair enough so a lot of simplifications are applied to this map, but plz comment none the less!

That's a pretty good selection of ten. Can you play them or are they NPC factions?

Some thoughts on factions and how you could incorporate interesting gameplay that lets the player encounter interesting history:

• It might be further south than you're intending to go, but the Mapuche have a dramatic history in the colonial era, quickly developing a cavalry on par with the Spanish and therefore retaining their independence. That's interesting from a gameplay perspective, the faction at the border of the colonizer's influence who uses that opportunity to adopt the colonizer's military technology before they can be conquered.
• It wouldn't be a "large area" faction until the later game, but I think the Garifuna would make a very interesting faction to fill the gap between the Maya and Chibcha. Your players will come to the game with preconceptions about the roles that Europeans, Africans, and indigenous factions will play in Caribbean history, but here's a faction of people of African descent, with a Carib/Arawakan culture, expanding and colonizing the Central American east coast.
• You don't have to put "Maya" in quotes; the postclassical Maya states are just as Maya as the classical Maya. I'm not a fan of the popular narrative of the postclassical Maya as the "scattered remants of a fallen empire" -- the classical Maya weren't an empire either -- but I see where you're going, that you don't want to imply that what the colonizers encountered was the popular conception of the classical Maya at the height of their population, economy, and political influence. Maybe you can treat the area as having two Maya-culture factions, the Yucateco in the north and the K'iche' in the south.
• The interesting gameplay story about the Aztecs is hard to capture in the absence of their neighbors, like the Tlaxcala or the Totonaco, in conflict with the Aztec and eager for new allies. That might give you something else to put in southeastern Mexico if you don't want to give the notion that Mesoamerica was Aztecs on one side and Maya on the other.

They are NPC-factions only.

Yeah I know about the Cherokee area is smaller (this goes for other tribes/factions as well) but I dont want to split them up too much. So maybe call the faction something more vague, like a suitable language group used as "nation name" for an eastern North-America faction?

Thanks for the feedback! Anything more is always welcomed.

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The Cherokee, Seminole, Choctaw, Chickasaw, Creek could maybe be grouped together as a "Mississippian" faction. (Historically, they were called the "Five Civilized Tribes", but I wouldn't use that term now.) But it's ahistorical (like some of these tribes were enemies of each other). Again, maybe this is an opportunity for several factions who have independent AI controllers but the same Culture modifiers.

Having a Cherokee faction is interesting for many reasons, one being that it gives another dimension to the European/African/Indigenous interaction triangle in that some Cherokees owned African slaves. (Various Europeans and Euro-Americans had encouraged slaveowning as a component of the adoption of a "civilized" economy.) I wouldn't inflate this too much (e.g., giving the Cherokee the same slave-based plantation economy as the colonizers), because the vast majority of Cherokee didn't own slaves, and you don't want to enshrine one kind of Indigenous/African contact in the Southeast to be the "norm" when it wasn't. But there are ways to work this interaction into gameplay. Some escaped or freed slaves were welcome in Southeast indigenous communities (resulting in, for example, mixed-descent Afro-Choctaw towns), but some escapees were re-enslaved or resold to their white owners. That kind of random "roll" mechanic could be a way to illustrate the chancy fate of an escaped slave in the U.S. southeast.