I think it has to be something that poses an existential threat to human life on this planet, so cars (and other inventions dependent on fossil fuels) is a pretty good pick for the top of the list, IMO. I saw someone in the comments pick animal agriculture, and that, too, contributes to the existential threat of a warming planet; so that, too, feels like a good pick for the top of the list.

For me, though, nuclear weapons has to be the worst thing we've ever invented. No other invention is capable of ending human life on this planet so quickly and so thoroughly.