I think it's largely the interface, at least in my case. For example, I have no difficulty sorting out RDS, Carrara, 3DS Max, Lightwave (well... a little Lightwave) and the like, which despite their myriad differences have the same basic setup and way of doing things, but when it comes to something like TrueSpace or Amapi, which also share properties, I generally either end up blithering to myself or attempting to fling expensive pieces of hardware within half an hour of even the simplest task. They just require a completely different approach, one that I at least am not too good at sorting out.