Personally, I detest mash-ups, for the reason that they often become train-wrecks because no one knows what they are doing. For example, my group prefers to make obnoxious combinations- games that rely completely on chance to hit people, with the gurps damage system, with the bonus damage for firearms. This has led to every combat dragging it's heels. The time we played a proper system, even for the first time, the rules were pre-documented, so they were interesting, if not speedy.
On the other hand, when you do a mash-up, you have to rebalance the system. You have to account for changes. It makes every combat into a beta test. Nothing kills interest faster. For the example above, I always avoided combat because it was the least fun part of the game. I would rather poison then take the chance of my shot missing because I pulled a spade when I needed a diamond.
Mash-ups are like beta-tests, they require a long string of testing- and even then, may simply fail to be fun, no matter how good the idea looks on paper.
I only mess with rules when it is for the benefit of play- not because it looks like it might be cool. The rule of cool carries you only so far, and the rest of the way is carried by dragging your players through the hell of whether or not your doing fatigue penalties correctly, and if they should be changed after the battle.