Thanks for the link. I do already plan to use insulated flex duct on each leg. I've already done so on other parts of the house and the difference is remarkable. Even just stretching out a length and trying to talk through it with a friend gives you a good idea of what it does.
I don't think I need to go as far as building dedicated mufflers as suggested. In a way I feel that I would already have that since there would be no constant cross-sectional path from one room to another. Sound would first travel through a 6" round duct, then through a much larger trunk (3-6 times larger), then another 6" duct. In many cases you add a 3x14" rectangular duct into the line.
Anyways, the main question is whether I want to consider moving the trunks to save headroom and possibly improve soundproofing. As mentioned, I'm leaning toward keeping the runs as they are since I feel like shortening them would likely make the sound problems worse, and at best I'd only be getting back SOME of my ceiling, not all.
One compromise I could consider is kicking the smaller 8x12" supply to be right next to the return, rather than having that big space between them.
Then, if I'm not moving them I need to box them in. The question then is what is the least-bulky build style. Do I need to worry about framing/drywall touching the ducting (squeaks?). Should I wrap the ducts in something first? How would I box in the tops of the trunks if they're installed against the joists?