Although the idea has been sparsely used here, Fiction is crawling with the idea a serious plague can strike the World after the 1920s devestatingly, where 20%-90% of the population dies-off (like in The Stand for instance).
How plausible is this?
Pennicillin and antibiotics have certainly revolutionized medicine, and a better idea of the microbes causing the plights have helped stop many infections. On the other hand homogenization through travel and trade brought our diseases world wide.
IMO These diseases couldn't cause spectacular die-offs, reasons listed with them:
Ebola, AIDS, and Other Bloodbourne Diseases - Spreading through blood and some other bodily fluids is not really effective in transmission.
STDs - You are going to pick out promiscuous stragglers, making everyone watching their suffering puritanistic, which creates a lack of bodies for the disease.
Smallpox and Polio - Both are declining naturally (Smalllpox was simply helped by Vaccination regimes)
So Who would you think would be good canidates, and how plausible would it be?