Firstly, you are correct in identifying infectious disease as an important factor influencing the population makeup of North America during this period. Old World diseases such as smallpox did cause significant damage to indigenous populations with lower immunity to these kinds of illnesses. While this is generally acknowledged, there is still some disagreement as to how the process played out, and what role European agency played in it.

As to the rest of your question, there are several things to keep in mind both about the Americas pre-colonization, and the nature of European settlement. To be clear, from here on out I'm going to focus heavily on Virginia and on the Chesapeake, since that's the region I know the most about, but we can still draw some important lessons from these examples. One of the most important to acknowledge is that when we're talking about indigenous peoples, we are talking about a lot of people organized into different groupings, not all of whom got along with each other. The categories of "indigenous peoples," "Native Americans," and "First Nations" exist only because European settlers arrived later and it became necessary to draw distinctions between groups. Colonial era indigenous peoples by and large did not think of themselves in such terms, and there were groups of native peoples who had long-standing rivalries with each other. One of the better known examples would be the conflicts between Algonquin and Huron peoples in what is today Canada and the Great Lakes region (as long as I'm thinking about it, the 1991 film Black Robe set in 17th century New France illustrates this quite nicely, if you haven't seen it).

To go specifically to my Virginia example, when English settlers arrived in 1607, they walked right into an already complex political order. The people who already lived in the region, with some exceptions, spoke Algonquian dialects, and were subject to the rule of a paramount chief known in our sources as Powhatan or Wahunsenacawh (spellings vary). This polity ruled over a collection of different tribes and villages throughout the Chesapeake Bay region, and not all of them were subject to Powhatan entirely by choice. The arrival of the English adds a new player to the game. The English could function as new trading partners, and it's possible that Powhatan sought to incorporate the English as vassals into his domain. This is similar to one interpretation of the famous and oft-fictionalized story of Pocahontas "saving" John Smith from death in a Powhatan village. There are now some scholars who think that what Smith was actually participating in an adoption ritual that incorporated him, on the Powhatan understanding, into local kin/power networks, and that Smith entirely misread the episode. To some tribes on the margins, the English could function as a counterweight against Powhatan influence. When the Powhatan did organize a coordinated assault on English settlements in 1622, some of the English settlements survived because some of the local tribal groups refused to cooperate, and in some cases warned the English in advance. The English were as much a potential asset as a potential threat. Often forgotten in this story is that when the English set up the Jamestown fort near the Chesapeake and encountered the local tribes, the English were not the first Europeans to have settled there. We now have pretty good evidence of a Spanish mission post that been established by Dominicans friars in the second half of the 16th century, and they were no longer there by 1607 because the local tribes had driven them out. When the English arrived in the Chesapeake and encountered the Powhatan, the Powhatan already knew about Europeans and had dealt with them before. This was not something entirely new to them.

Also important to acknowledge is the very ad hoc, scattershot nature of English colonization on the Atlantic coast of what is today the US. In the 17th century in particular, colonization in English America was largely the province of chartered corporations and individuals given special letters patent by the Crown. It was not a centrally managed process, and the settlements that cropped up were not necessarily intended to be permanent settler colonies. Unlike the English settlers in New England, who largely came in family units, settlers further south in Virginia were predominantly male, and were serving in what was perceived at the time to be a military-commercial venture. It took some time for the social and cultural institutions associated with a permanent civil presence to emerge there. What this means for us is that nobody was necessarily assuming a permanent settler population. As far as the indigenous peoples were concerned, there was no reason to assume that the English would gobble up the interior as they eventually did.

Even if native peoples had the complex institutions that could coordinate actions across tribal boundaries to drive out Europeans, the motivation simply wasn't there at first. As Europeans gained more of a foothold, there are later attempts at consolidating actions among tribes against European settlement - King Philip's War being an earlier example - but a lot of this occurs after European settlers had already established themselves on the coast for a couple of generations. If indigenous peoples did not wipe out English settlers when they had the chance, it was simply because there was no reason to. They had no reason to think the English would come to completely dominate the interior; they had no access to any kind of history that would lead them to think this was a serious risk.

Readings

Alan Taylor, Colonial America

James Horne, A Land as God Made It: Jamestown and the Birth of America

Karen Kupperman, Indians and English Facing Off in Early America

Daniel Richter, Facing East from Indian Country: A Native History of Early America

Colin Calloway, New Worlds for All

Helen Rountree, Pocahontas's People: The Powhatan Indians of Virginia Through Four Centuries