I have done a few ex-EU (not many) at the start of a holiday. There is one element I've consinstenly enjoyed: spending a night/morning in a European city as a way to start unwinding in preparation for a longer journey to the final destination. Once we even built in a long stopover in DC in the middle of the trip, which was great.

Obviously it does not suit everyone nor it's always possible. However, it's something that we say we would do again, should we have the opportunity.

On the other hand, I find back-to-backs quite stressful!