Sure the contexts are different, and you can also look at the federalization of German states as yet another example with a different context, but not all of the factors are unfavorable. For example, the countries of the EU are already more integrated than the colonies were. Plus it's a very different time now, we've had the UN for a long time already, etc.

Also, I was surprised to learn how heterogenous the different regions of the US were from the very beginning, in origin, character and motivations. The Puritans, Quakers, Cavaliers, French nobles and traders etc.

This video explains why it's very likely to happen: https://www.youtube.com/watch?v=7yHJehbWiNo