Religion has changed in two and a quarter millennia, we don't worship Roman or Greek deities anymore either, maybe a few still do, but they are in the minority.
For me the what-if scenarios would rather see the Spanish conquistadors land in the Americas to find the mysterious Amero-Indian cultures defending their homelands with supernatural abilities (shamanistic, spirit, dark rituals - depending on the culture). Now you would have technology vs dark magic, civilisation vs brutality (depending on which side you were on), perhaps bring in a crisis in faith on the European side as they struggle to understand what/who they were up against....as information about these savages reaches the bastions of the dominant Christian churches.
That is the thing, the Spanish Conquistadors were human beings, not devils, they had a technological advantage over the Indians and they used it, because they wanted to enrich themselves, they Aztecs if they had that technological advantage would have used it too, if the technological advantage were reversed then their roles would be reversed as well. We know how the history between the Conquistadors and the Indians played out, that is all in our history books, and if you play in such a setting, there is a historic inevitability to it, if you reverse the roles, we just don't know what's going to happen, as that history hasn't been written yet - that is what makes it interesting. In a role playing game, the PCs are the ones who make history, what they do is important. In a purely historical setting, they are reduced to bit players working on some minor plot in the background, but here they can take center stage. The Indians aren't guaranteed to succeed, the natives aren't guaranteed to fail. The moment you introduce elements of fantasy, you have to decide which elements, and also whether gods are real and which gods. Are the PCs going to make history or are the Gods going to step in an interfere?
No need to please everyone for your home game and even if it isn't your home game you cannot please everyone.
Look at BBC's Troy Fall of a City bastardisation of history/culture continues and you have proponents and detractors on both sides.
We have limited knowledge of the Fall of Troy, and some point they have to make things up to fill in the gaps.