wikipedia, our friend...
http://en.wikipedia.org/wiki/Smallpox
The origin of smallpox is uncertain, but it is believed to have originated in Africa and then spread to India and China thousands of years ago. The first recorded smallpox epidemic was in 1350 BC during the Egyptian-Hittite war. Smallpox reached Europe between the 5th and 7th centuries and was present in major European cities by the 18th century. Epidemics occurred in the North American colonies in the 17th and 18th centuries.
So, a few thoughts (and I guess I'm not completely abandoning the thought)
I agree with iron axe as a force multiplier, and the sailing/fishing areas.
I wanted to disagree with the 'they had cities', but research proved me wrong. So sure, they had demographics, they did not have the population density of the european cities - but, as I am learning quickly, it all depends on what time you are considering.
Take Cahokia vs London England
"In west central Illinois, at the mouth of the Spoon River, they established a large town surrounded by smaller communities, and a large cemetery now known as Dickson Mounds. Near East St. Louis, Mississippian people built Cahokia, one of the largest Native American cities in North America-larger, in fact, than many European cities at the time. Cahokia was a political and religious center of Mississippian life."
"Archaeologists estimate the city's population at between 8,000 and 40,000 at its peak, with more people living in outlying farming villages that supplied the main urban center. In 1250, its population was larger than that of London, England."
In 1250... London was only around 25,000.
But just 200 years later, with the technological & sociocultural edge of London... even the 40,000 of Cahokia's peak in 1250 falls short of the 50,000+ in London, and the gap keeps widening in the years to come as London keeps growing.
But, consider London versus the richer, far vaster, environs of the Mississippian culture (Cahokia) when added to everything in between them and the Iroqouis confederacy, if the two were on level technological fields, and the edge is given to the Native Americans via the influx of a representative democracy and free market capitalism versus Londons Monarchy.
Ever played CivI, II, III, etc.?
Clearly, the Indians would have outpaced and outteched England (and thus, by extension, Europe) in just a few hundred years.
Now, as for disease... if they had the population densities (or greater) than Europe, yes they would have been devastated by strange European diseases... unless they'd managed to get contact w/ Europe/Africa and developed the immunities (one possibility)
Another possibility is that they could have their own diseases ready by the time the Europeans arrive, which would then have devastated Europe as well.
I lean towards earlier contact from west to east though.
Say 900-1000, influence from vikings brings technology to the Iroquois and other tribes. Social pressures within another 100 years accumulate into virtual city-states w/ representative democracy and the beginnings of mercantilism (which the natives had anyway, at least the beginnings of it). Another 200 years (1400) to unite/combine/merge other tribes across the vast majority of the Eastern seaboard & Mississippi River valley -- mostly seaboard due to sailing & fishing, but interior as well with more easily shaped wood (iron) and improved agriculture. Around 1400-1500, contact to S. America (Aztecs? others?) and full contact with Europe, along with disease and devastation (both ways I wonder?). With greater population though, are able to meet European colonization almost on equal footing.
At all possible, or still wildly implausible???