There are several problems with substrate including accidental ingestion, making it too easy for free-roam prey to hide, difficulty of cleaning and, depending on what type of substrate we're talking about, bacteria.
That being said, I use green moss as a substrate because I too desired a very natural-looking cage (to me, that's part of the joy of owning an exotic reptile). it looks very nice and it does have the added benefit of raising humidity, though I don't think it's very noticeable in the huge cages chameleons require. It's actually not THAT difficult to clean (especially if your cham potty trains himself to poop in more or less the same place as many chams do), but it does require pretty much taking everything out of the cage. I'm pretty sure eventually all the moss might have to be replaced (and at that point I may just use a plastic liner).
Aesthetically though, I feel like it can't be beat, so if you're willing to work with it, you might try checking that out.
