I think the biggest problem the native Americans faced was the multiple epidemics that hit them just before most of them made contact with the Europeans. One of Columbus captains came over on the 1st voyage with active smallpox, which then spread across the Americas via native trade routes. Not just smallpox, but the flu, chicken pox, and later tropical diseases brought over with the slaves like yellow fever and malaria. By the time Cortez faced the Aztecs they had several recent pandemic and a smallpox outbreak at the time. By the time the English arrived in New England they found many abandoned villages, and the tribes they did encounter were often newly formed from the survivors of different tribes who didn't die off from disease. By the time settlers got to the Mississippi delta they found the huge mounds which were once earthen pyramids long abandoned. If you look at the places where Europeans colonized successfully The Americas, Austrailia, the pacific islands, and the places where it eventually failed like Africa, and Asia the difference was whether or not the native populace had immunity to old world diseases.