Essentially what it says on the tin. The Mexica and the Inca were the most advanced native cultures, technologically, that arose in the New World, but both were fundamentally stone-age tech civilizations that didn't advance the same way their counterparts in the Mediterranean, India, and China did.
I've heard it suggested that the north-south arrangement of the continents themselves impeded things, since the east-west alignment of Eurasia meant that the climate stays the same along broad bands, allowing for ease of trade. But I question how much the advances of Europe from prehistory through to the AD's really affected the development of, for example, China and Japan, or vice-versa. While I understand that there was trade, it was very limited, and I can't into the idea that a significant number of advances passed along Eurasia in that way prior to the AD's.
I've also heard that weather was an issue; it's difficult to build a large civilization when every year might bring a major hurricane that could ruin everything you've been building. But India doesn't exactly get a pass on ruinous weather, and random, major flooding was, if anything, an impetus towards advancing civilizations in Mesopotamia. On a similar note, I've heard it said that corn just isn't as good a staple crop as wheat or rice, requiring much more work to maintain. But, again, that if anything seems more like an impetus towards advancing a civilization towards growing more and more corn easier, rather than a hinderance.
The third thing I've heard is that the mineral wealth of the Americas is simply harder to get to. Dunno much about that so can't comment.
And lastly, I've had it pointed out to me that civilization and the advancement thereof is largely random, a result of the right advances at the right time largely by mistake. Eurasia "lucked out" and the Americas didn't.
Which is the case? Or is a mixture of all four? Was there really anything actually impeding the growth of large, iron-age and beyond civilizations in the Americas, or was it just a matter of luck?