Living space vs having maybe a slight advantage of some convenience while on the road. Toad vs truck. Those are the only two issues that are important imo.
Since you're the only driver that amounts to getting out of your truck and walking to the fifth wheel door, opening it and going inside to take a leak. Vs getting up out of the MH seat and walking to the door to do the same.
Setup is such an overblown thing its not even worth considering. I could train a chimp to setup any rv.
Toad vs truck pick one I don't see the big deal but some people can't drive a truck for whatever reason.
Fifth wheels have far superior living space and internal storage. If you aren't traveling all the time then a MH's advantages become pretty minimal unless you are completely adverse to driving a truck around.