What should be taken into consideration when mixing Fluxx sets?
Mixing Fluxx sets is fun, but it will:


probably make the games take longer since you have half as much chance of getting a relevant keeper.  The more sets you add the lower the chances of getting the card you want will be.   With 3 decks your chances are 1/3.  With 4 decks your chances are 1/4.  And so on.  [Thanks to @SocioMatt for encouraging this generalization.]
get weird.  Some sets, like Star Fluxx, have keepers with superpowers which might overpower the other set you mix with it.  Reports indicate that Monty Python Fluxx doesn't mix well.
Stoner Fluxx and some non-English Fluxx editions have different backs which might let your opponent figure out which cards you don't have more easily.