How long is a piece of string???
The subframe being stepped or flat is not really the issue if you are concerned about the truck chassis developing cracks. It's how the subframe and chassis are connected which is important.
There are many threads on here about the pros and cons of different mounting methods, but how you decide to do this really comes down to what type of box you are putting on the back and how heavy it is.
I chose to use a straight subframe for numerous reasons, but that does not necessarily make it the "best" way to do it. It was just what worked for me and the design I wanted to use.
As difficult as it might be, you really have to know the big picture before you can concentrate on the finer details.
Whether or not you keep the spare wheels where they are is a typical example of this. Are you interested in having a pass-thru? If so then the answer would obviously be no. Will having the wheels there affect the camper body design adversely? With the camper body in place, how easy will it be to access the spare wheels? And I could go on (but I won't).
It's your baby and the design is totally your choice. All I can really suggest is browsing through the numerous posts here in this forum and see what might work for you, and what won't. In my experience, the planning takes considerably longer than the actual manufacturing. Making stuff is the simple bit...