I have a 1Up USA Super Duty. I carry an R&M Nevo with front and rear fenders. I do not have or use the optional Wheel Stop. I do have and use the optional foam fender protector on the rear fender only and it works great. I have no problem with rear wheel centerline hanging off the tray as you have shown, but my bike has 26" wheels which probably makes a good bit of difference.
My rack and bike is often on the back of my GMC Acadia which is being flat towed behind a class A motorhome. No issues with this set up.