This is an idea that I've been floating around lately. What if, during the American Revolutionary War, things go much worse for the Americans? They still end up winning in the end, but in the process they possibly lose claims to the Northwest Territories, northern New York, or maybe even the South.
Maybe with a rebuffed expansion, the US looks in on itself, instead of outward. The issue of slavery is slowly pushed out, as the views on slavery continue towards eventual emancipation. Maybe have an independent Louisiana Territory, with chunks of it taken by Canada and the British. No (or little) American migrate into what was the Empire of Mexico, so possibly no Texas Revolution (unless Louisianians, or French, move in).
Just a bunch of thoughts on my part. Any ideas?