I think one needs to consider the level of social development of Europeans at the time of first contact with Natives. Most Europeans were illiterate or semi-literate farmers or landowners with very narrow horizons, and the more educated part of the social and political elite was a very narrow group. Many of the people who first came to North America were traders and adventurers, some of them failed members of the social elites but others very rough individuals. And the farmers who first settled in North America would generally have been poorly educated, probably with narrower horizons than most of the Native people they met. One advantage they had was iron tools and firearms, but the main advantage for settlers was the initial lack of immunity by Natives to European diseases - that really thinned the ranks of the Native people. But during the early period, it wouldn't have been difficult for the two cultures to merge if either side had wished it - remember that most Native people in eastern North America were subsistence farmers, just like most Europeans, but without the same tools or livestock. I doubt if either side was interested in integrating, for the most part, but in the southeastern U.S. there were some Native tribes, especially the Cherokee, who adopted European ways and tried to become part of American society. They were forcibly removed to the west, with great loss of life. It's one of the most shameful episodes in American history. And here in Canada, although British and later Canadian authorities did try to accommodate Native people to some extent, as long as they didn't prevent white expansion, many white individuals were quite hostile to Native people and in some parts of the country they still are.
Of course, Native people aren't blameless, and they're the ones who now cling to the reserve system, and they often have a very negative attitude toward white people. Racism unfortunately seems to be part of the human condition. We tend to favour our tribe, however it's defined, and to fear "the other", however it's defined. And that less than admirable human trait has certainly been a major factor in relationships between Natives and others here in North America.