The Missouri compromise does not happens and because of tensions between Free and Slaves States, the Slave States secede and form the Confederate States of America. The separation is peaceful and the border to the West is set to be the Platte river, following the South Platte River to the border with Mexican lands in Colorado.
Is this possible?
How would North America develop? What's going to happen to Mexico? The USA will expand to Canadian great plains? Will the CSA have a Pacific port?
A long time ago, there was a pretty interesting TL (elsewhere on the web, not here) that used this POD. It was by a guy named Tommy Gehring, but I can't remember what it was called and it doesn't seem to be online anymore anyway.
From what I remember, all the slave states seceded and became the Confederation of American States (CAS). The CAS fillibustered its way into Texas and conquered California, while the USA eventually conquered all of Canada. The CAS ultimately conquered most of Mexico too, and tensions between the CAS and the Mexico remnant (allied to the USA) caused a World War I-analogue (beginning in 1914, I think; up until then, the two Americas actually never fought a war IIRC). The war pitted the CAS and its allies the UK and German Empire against the USA and its allies France and Russia, and it ended in the CAS victory. After the war the USA became a fascist dictatorship and the CAS went nuts conquering South America. The author finished it as far as the 1940's, then it stopped.
It probably sounds pretty ASBish, but it was very well done (it even had maps and flags!), and I remember really enjoying it. It must have been, oh, ten years ago since I read it, though.