I have talked with a few people and they all recommend using 2x2's. Since you are not building the trailer (walls, roof, etc), but rather a box within a box, you don't have to build to support weight or wind. I am building something very similar, and plan to frame it with 2x2's everywhere except the corners of the LQ, where I will use 2x4's.
53' toyhauler build - Pirate4x4.Com : 4x4 and Off-Road Forum
As to your question about the toilet, I would place it where the floor drops. (as you described above). This will allow the straight drop for the sewer, and allow the tank to be located behind the tractor (instead of over it). This would make for easier plumbing and shorter too.