And if the numbers given by some here about Native American populations in the millions (15,000,000!?) are true, how did the White Man ever manage to penetrate a population greater than his own? Whiskey, smallpox, and guns? Exploiting tribalism among the Natives? Because if true, then making a Native American National Entity was impossible. They didn't speak the same language, and were blood enemies as often as indifferent as often as allied. But NOT united.
Yes indeed, I think that any united Indian TL would need to deal with the problem of how exactly you get all these disparate tribes to unite. Heck, just look at the difficulties the Greeks had in uniting against the Persians -- at the time of Xerxes' invasion, the majority of Greek city-states were either neutral or pro-Persian, despite the fact that the Greeks had far more in common (in terms of shared language, culture, history and religion) than the Native American tribes did. Or look at the Gauls versus the Romans, the Germans versus the Romans, the Britons vs. the Saxons, the Spaniards vs. the Moors, the Christians vs. the Ottomans, the... Well, you get the point. Even in the face of an obvious threat, and even with the advantages of having a common language, culture, and/or religion to bind people together, it's often hugely difficult to get independent countries to properly co-ordinate their efforts over any period of time.
Of course, it wouldn't be impossible to do a plausible scenario in which a large empire manages to take control of all or most of the Mississippi basin, along the lines of Imperial China or a scaled-up version of Ancient Egypt. That way the entire area would eventually become a single cultural and political bloc, able to present a united front to the Europeans when they finally reached them. Such a scenario would require a POD centuries or even millennia before Columbus' discovery of America, though.