The Indians left significant constructions in the four corners area, structures which abased on sophisticated astronomical knowledge. Theer were about a thousand years ago, a large concentration of people in the vicintiy of St.Louis based on agriculture. Such things did not last ,but they existed at one time or another. Most of the Indian nations east of the Mississippi depended on the cultivation of corn, and the white found huge fields on either side the the Ohio. This was supplemented by hunting, and it is speculated that the reason why the population did not grow was a lack of meat animals and a subsequent lack of protein, so that when an area did grow, it soon reached a limit. The English found a significant population in the Chesapeake area, and organized un the Powhatten into a confederacy.
The first settlers existed by trading with the Indians for their corn surplus, but as John Smith tells us, because the Stllers ran out of food, they had to resort to raiding the indians for what they would not trade.
Below the Rio Grande was different because the Mayans and the Aztecs had actual cities and other organized manifestations of cultures with sizable populations. Not true in America above Mexico.
There were also plentiful Leni Lenape (Delaware) indians in the Philadelphia-Delaware settlements. Philadelphia's map is full of Indian names, such as Conshohocken, Wissahickon, Moyamensing, Shackamaxon, etc.