With an adequate tow vehicle, proper equipment, and proper hitch, I don't think there is a significant difference in handling either way. They are different, but once you get used to your rig, I think they are about the same.
I think it mostly depends on your RVing lifestyle and what you like to do and your budget.
Fivers have more storage space, fancy floor plans, and interior headroom. On the downside, they cost more, you have to climb a lot more steps, and they are generally heavier, higher off the ground, and taller so they require a bigger truck and sometimes limit the campsites you can get into. As mentioned, they also limit the use of the bed of the truck - both with and without the trailer hooked up because the hitch remains in the bed. A bigger truck - usually a dually - is a little more difficult to find parking spaces for than a single rear well vehicle.
We spend a lot of time surf fishing, and like the van because we can securely store our 12' surf rods in the van without taking them apart. The van also has lots of room for the dogs, grandkids, and whoever else may come along.
As someone else said - think of what you might like to do while traveling, and go look at lots of different floor plans of both types of trailers. You will probably know when you find something that fits, then you can match it with an appropriate tow vehicle.
Bill & Kate - Stone Harbor, NJ
w/ Bailey (standard poodle) and Zeke (partipoodle)- both rescues
2018 Ford F-250 Super Duty Crew Cab w/ 6.2L gasser
2014 Forest River Wildcat 272RLX fifth wheel