The invention of agriculture.
Think about it: it led directly to
- Humans eating stuff they're not evolved for
- the beginnings of surplus hoarding, hence money and exchange economies and the beginning of social classes
- people being tied to a particular bit of land - hence feudalism, classism, nationalism
- backbreaking toil for whoever was the underdog in any human group
- ruin of the environment, species extinction
- earlier and increased fertility (i.e. breeding 'til you drop) for women
- formal concepts of marriage ('nuff sed!)
No wonder some social scientists call it the 'Great Leap Backward' in human evolution.
Plus side, however: bread. and rice. and barley. and pommes dauphinoise an' that.