Well, for one thing you don't even have to have a backup cart in the system. That means seriously improved battery life and if you like to suspend your system rather than turn it off it also means it will be far more stable for far longer. It's also exponentially more convenient. You can organize icons on your home screen -- even using folders to organize further. For going through Gateway or a clone you have to hit select, wait, use that really slow menu, select one, wait, wait, wait, then start the "cartridge." Changing means going through that all over again. Organization is essentially nonexistent -- the best you can do is use a utility that changes order appearance somehow (I haven't figured out how it sorts -- I think it's timecode based or something but when I tried touch it didn't work.) That leaves you with one long list if you use only it. Sky3DS is even worse since you don't get the multirom menu at all.
Also, CFWs like rxTools can only use CIAs since they don't have a cart to load ROMs through.
EDIT: Darn. I keep trying and retrying. I don't know why it is, but I can never get an undub to convert. Everything else does, but undubs fail 100% of the time for me. :-( This time oddly enough I get a black screen that says "an error has occurred" requiring me to shut off the system whereas normally it just fails to build though, so that's interesting.