For starters, some Europeans somewhere were eventually going to "discover" the Americas. Russian explorers eventually poked around Alaska and would have come from the other direction. Even if Columbus hadn't wandered over in 1492 convinced that he had a short cut to the Indies because the world was smaller (not rounder, smaller) than everyone else thought, ship building technology was approaching the point where such voyages were possible. Make it possible and _someone_ will do it.
Bad luck for sure it was the Spanish, right in the middle of their most arrogant conquest period. (IMO as descendant from victims of the Inquisition, the Spanish don't get nearly enough bad press in this.) There is nothing like feeling that God and History are at your back to push you into high gear on stomping all over everyone else. In the time that Columbus was discovering America, the Spanish were also attacking North Africa (having finished taking Iberia), waging war in the Mediterranean, exiling Jews and Moslems, and torturing people suspected of being secret Jews and Moslems after the fact. Not the ideal selection for First Contact.
Most of what actually pisses off North American tribes really has nothing to do with Columbus and everything to do with U.S. conduct post-Revolution. For a considerable period of time, settlers in North America and in Canada got on reasonably well with Native Americans. There was, after all, a great deal of room (especially after the mass plagues generated by contact with Europeans in South and Central America migrated up to NA via the trade routes) and settlers had lots of interesting things to trade and learn.
What really killed Native American tribes in the U.S. was our open immigration policy. More people, more pressure to expand. What few efforts made to actually limit and control westerward expansion were pretty useless. So the federal government would inevitably go back on its treaties, rationalizing along the way, helped by those segments of the population and in government that were all about the Manifest Destiny thing. As noted above, the belief that God and History are at your back do not make for tremendously good first contact, or even continuing contact.
So I guess what I'm saying is, the history between 1492 and now is complicated, and resists simplistic narratives. It's not enough to know people suffered or profited. The who and why matter a great deal -- if only to avoid repeating the same patterns over and over. Hardly a momentous insight, perhaps.