Some word-of-mouth gripes I've heard with 4x10 setups suggest that there's only so much gain you can use...it can only get so crunchy. I don't play with very high gain so it wouldn't bother me, but I've had friends who are into metal complain about that.
The only thing I've ran into is the expense of 4 new speakers haha. but you'll have that same problem with any 4 speaker set up.
My 4X10 is my favorite cab and it's built like a tank. It will handle gobs of gain but I don't use it that way. I've loaded it with tone tubby alnico on the bottom and the new Celestion Gold 10" on the top.
The most noticeable difference is the bass tones which are very prominent and tight but not overwhelming.
I have a Marshall 4x10 cab that sounds absolutely awful. Farty bottom end.
I have a Marshall 4x10 cab that sounds absolutely awful. Farty bottom end.