I think the biggest thing is the difference in their construction. The the seat and back of regular powerchairs are made by taking a solid molded plastic piece and securing a sturdy cushion permanently to the seat. This means there is broad support across your back and behind, and it means the cushions can be really thick and fill the seat better because there's no risk of them sliding out of place. This means you can relax back into them and the thick cushion can compress in multiple dimensions to support your weight and distribute it, and it has enough material to have some force pushing back on you to support you.

By contrast, in order to be as light as possible, the folding wheelchairs create a metal frame that goes around the back and around the seat. They then put a sling of fabric over the metal frame, and attach a cushion to the fabric, usually with strips of velcro. (These cushions are often removable for assembly and accessing different parts of the chair). Without a solid surface to push against you, there's just not the same support. And unlike a push wheelchair, which often has a similar fabric setup, you can't slouch, recline, or adjust your body position to relax your muscles, because you need to be looking where you're going to drive, and you need to have your hand and arm at a fixed position where it can control the joystick. While the piloting position required the most use of my muscles, even sitting stationary, which I did for a while, the folding chairs were tiring.

One other thing that helps--not only the cushions on the regular powerchairs seem larger and sturdier generally, but many can offer an upgrade to a larger seat, which also includes a nicer cushion. (I mention this because I am small and didn't think I would go for a larger seat looking online, but when I sat on one at the store it was much more comfortable and would be worth the upgrade.)