I'm honestly convinced that the Americas would have eventually repelled the European invaders if the introduced (and intentionally spread) diseases weren't so devastating. Guns and metal armor are pretty good in warfare and all, but the size of the army required to subjugate millions of people across varied terrain where the invaders are wildly unfamiliar with the land and how to live in it while the defenders have been present for thousands of years, are very familiar with the land, have established warfare traditions, quickly adapt to introduced technologies, and have allied with historic enemies to repel invaders? Does not tend to go well for the invaders.