You're a bit off the mark for a couple of things, but I'll address the impact of disease on native communities in the Americas. The short answer is it was devasting, short term and long term. Millions died and it is almost impossible to measure the true impact of death on this scale.

But the one area I do want to address is this idea that Europeans faced relatively little resistance from native populations. This could not be further from the case. Many native communities fought back once it became clear the Europeans were looking to conquer. Popay's Revolt is a great example of a successful uprising/expulsion of European invaders. They were able to not only drive out the Spanish but also were able to influence Spanish policy towards their homelands when the Spanish did eventually return. Other examples would be the Caribs, the tribes of the Great Plains, and the events of the Black Hawk War in present-day Wisconsin/Illinois.

These attempts at resistance resulted in varying degrees of success, but are just a small portion of the resistance native communities showed to European conquest. You would be hard pressed to find any region of the Americas that did not have native communities attempt to resist, and this unquestionably impacted the success of European efforts to conquer the New World. With resistance lasting from initial contact through to what is essentially the present, it is wrong to think that anything would have made the people of the New World easy to conquer in the manner you describe.

Tldr: disease killed millions and had an undeniable impact on native communities, but you have to remember that there was resistance to European conquest that lasted well over 400 years all over the Americas.