Does it make any difference if you are hauling more than one horse at a time for the level of difficulty? I would think it could be good or bad since they would have company, but also one could upset all the others too.

I think the most logical argument might be weight distribution if you had two equally heavy horses, but two horses could just as easily both lean to one side as one. I think for the most part its the maneuvering of the trailer thats difficult so long as your horse is trained and calm while shipping.

We used to have a pretty big horse trailer and would haul 4 horses at a time. So I'd say you will probably have problems hauling 4 horses in a small horse trailer.
Read the owner's manual, I'm sure that will help.