Eh.
Unhealthiness would fit best a persistent problem. Pagues, however, break out at certain intervals, every 30-80 years depending on the time and place. Really bad plagues are what are highlighted in our textbooks and should be what we attempt to emmulate.
A sudden drop in population seems a better way then unhealthiness. While some technologies, like the Germ theory or proper Quarentines, do improve responses to diseases, they have certainly not been stopped them. SARS, AIDS...
The greatest loss of life from a 'single' event in World History was not the Black Death, nor WWII, it was the Spanish Influenza in 1918-19.
I would like to see a complex disease system, perhaps using one or more dummy religions (when the 'religion' enters your city, X% die but the city is now immune); but, a very complicated algorithim involving troop movements and contact establishment would be 'more' accurate.
Dummy religions would be our best bet, we can implement it without creating many new subfunctions. I have seen elsewhere discussions about genepools and the normal exchange between cities with the movement of troops disrupting the natural flow and bringing 'exotic' genes to cities which cause plagues that kill % of people (the % depending on how 'exotic' the genes are). But, this can be saved for a mod solely dedicated to disease and/or Civ5, or 6.