@Justicar Probably the biggest yeah due to the sheer amount of people affected, but historically I would expect it to be the third most relevant.
The black plague that killed most of the poor europeans and led to the renaissance and the new golden era of civilization was the second most relevant since it changed how the world worked.
Rome's collapse take the 1st because the world went from science, toilets and running water to literally over 1000 years of the dark age.