This one was stunning. The death toll was 830,000. No, I didn't misplace a zero. That was close to a million dead overnight and it was 4.5 centuries ago. http://en.wikipedia.org/wiki/1556_Shaanxi_earthquake
Santorini probably had a bigger effect on human history, basically wiped out the Minoan, Greek and Egyptian cultures.. we might have been walking on the moon 500 years earlier without losing them.