Fretlesses are built for running clean... ideally through a '18 subwoofer (real lousy for heavy slapping, chord raking, fast/hard picking, etc. [which is why bass cabs more often come with '10 speakers] but otherwise ideal for tone and presence). So you get that smooth growl that makes tone freaks pucker their nether-regions, buuuuuuuut... switch on the distortion and overdrive and it sounds more like a 400 lb. vegetarian farting on a pinwheel. Chords, whatever slap/pop can be done, and lots of compression can help... but fretlesses are meant for slides and bends (ohhhh yeah) so hopefully if I had a second amp, running clean with no effects or anything, I'd be able to pull off what I'm after.
But all that, of course, is for another board.
For guitar, I think if I kept the effects limited to the main amp and left the other two 'pristine' it would work without too much... uhhhh... overwhelmingness. I'm kind of a minimalist when it comes to effects anyways, unlike this guy, the infamous Agata of Melt-Banana:
My brother saw them live down in San Diego... says he was stomping on some pedal or another every two or three seconds, and instead of a slide was using what my brother described as "a piece of metal he found on the ground." It sounds like... a grizzly bear trying to eat a Moog machine.
Now... if I only had the cash!!!
A slightly more budget-friendly version of the above is a Traynor 2x12 for main (from what I understand, similar to Fender but better at dirty, whereas Fender is better at clean), a Fender 1x12 for clean, and... maybe something by Peavey in 1x12 for extreme. Yeesh... that's not too much friendlier....