What if... several or all of the US states become their own countries?

If the US suddenly spit up but retained the current friendly relations between states as is currently there? I don't think anything special would happen. The US is/was a great place (maybe the best) and people wouldn't want to disrupt that. So no annexation wars, trade would resume as best it could and the country would either reform again or become like the EU. Why rock the best boat out there?

If whatever caused the split also soured relations between the Divided States of America then yes you'd be in trouble: land disputes, refugee crises, impoverished states and resource wars. But really the biggest problem is not the divide, but the event that caused such a nasty split in the first place - that's one spicy lump of phlebotinum

Would the Mason-Dixon line make for a "natural" division point if the USA were to start to splinter? Given the history 'n' all.

In my Cyberpunk role-playing universe the USA has balkanised into several smaller countries, some of which cover more than one state. I've got the traditional Confederate States maintaining their historical allegiances - the South didn't "Rise Again" so much as "Fail To Fall".

It is more likely the states would simply join a few neighbors to form a new nation. There is too little benefit and the nature of our modern method of shipping goods around would make being one state is a country a difficult prospect without some at least friendly ties.