Here's a darkly hilarious one, because you could do it by accident: give smallpox to the native Americans a few hundred years early. Right around 1000 AD, show up to shake hands and teach metallurgy or whatever, maybe planning to jump-start their resistance to colonization... and their resistance to slaughterhouse-borne diseases, the hard way.

This would of course completely fuck up their population numbers, much the same as would happen in Europe in the 1300s. But by the time Columbus showed up to be the absolute worst person who could possibly discover a new continent, they'd be largely recovered, and they'd get to trade whole new strains with the seasick lemon-sucking weirdos who kept asking where the spices were. The returning ships would offer tomatoes and potatoes and another Black Death. Hopefully preventing Malthus from being such an influential bastard, and causing the first engineered famine in Ireland, whose population did not recover from the potato famine until this century.

New England colonies would presumably still take hold, but wouldn't steamroll all the way to the west coast. Hopefully they'd be limited and northern enough that slavery is less prevalent, less absolute, and - ironically - still a matter of trade. Because what ended the triangle trade to America was the treatment of African captives as livestock to be bred. The politics of this alternate timeline would be hilariously complex compared to now, and probably result in more and stranger wars than we can imagine, but there would be so many averted times where atrocities happened, effectively unopposed.