I gave this some thought, and it occurred to me that smallpox, even after co-evolving with humans for at least 10,000 years, still had a mortality rate comparable to Ebola today, a similar incubation period, and a similar amount of time before the patient was incapacitated.
edit:
It seems that this wasn't accurate. From wikipedia:
>In the United States and South Africa a much milder form of smallpox, variola minor, was recognized just before the close of the 19th century. By the mid-20th century variola minor occurred along with variola major, in varying proportions, in many parts of Africa. Patients with variola minor experience only a mild systemic illness, are often ambulant throughout the course of the disease, and are therefore able to more easily spread disease. Infection with v. minor induces immunity against the more deadly variola major form. Thus as v. minor spread all over the USA, into Canada, the South American countries and Great Britain it became the dominant form of smallpox, further reducing mortality rates.
In regards smallpox there were multiple strains circulating at any point in time and some were more deadly than others. Which ones spread at any point in time depended on both chance and the particular selection conditions in the population. In populations with high levels of immunity (either natural or acquired) the more mild strains tended to spread, while in populations with low levels of immunity the more lethal strains would tend to spread (lot of complicated reasons for this).
Your general idea is correct though. Just because a disease has been in a population for a long time does not means that it is harmless, not are all new diseases dangerous.
edit:
It seems that this wasn't accurate. From wikipedia:
>In the United States and South Africa a much milder form of smallpox, variola minor, was recognized just before the close of the 19th century. By the mid-20th century variola minor occurred along with variola major, in varying proportions, in many parts of Africa. Patients with variola minor experience only a mild systemic illness, are often ambulant throughout the course of the disease, and are therefore able to more easily spread disease. Infection with v. minor induces immunity against the more deadly variola major form. Thus as v. minor spread all over the USA, into Canada, the South American countries and Great Britain it became the dominant form of smallpox, further reducing mortality rates.
https://en.wikipedia.org/wiki/Smallpox#Other_history