Over the years, I've seen all manner of interesting emails, blog posts and so forth, discussing replacing parts of the 5X system with an aspect from another game.
For the purpose of this discussion, I'll focus on Five Leagues. I've seen or heard from people replacing the combat mechanics with Thud&Blunder, Song of Blades&Heroes and even a very ambitious Rangers / Five Leagues mash-up. I'd be shocked if there wasn't a Mordheim / Leagues mash-up out there.
While I always try to provide for a fairly modular structure, I think it's super interesting that people have been able to do so with relatively little difficulty. Of course, you have to adapt things like experience and rewards, but if you are already on the road of writing your own mash-up game, that's no great challenge.
Of course, it's difficult to tell which mash-ups comes from someone being unhappy with the Leagues combat system, versus someone being unhappy with the campaign in the other system. Or they just wanted to see what would happen, which is a very "gamer" thing to do!
In any event, I fully support it and I think it's really cool. Definitely let me know if you get up to anything like this.