Deb here: We've had a Class C and a 5th wheel. I could drive and hook up both; and backing up either one wasn't a problem, so here's my advice:
If you see yourself going to a single campsite and staying for the weekend or more - a 5th wheel gives you the most room, and leaves you with a vehicle to drive (although generally a big beast and unwieldy in small spots). Several years ago, we got caught in the Great Atlanta Ice Storm pulling our 5er, and I can attest to how well they pull even under dire circumstances.
If you are leaning towards sightseeing - maybe a different RV park each night - you just can't beat a motorhome for ease of travel and setup once at an RV park. And as gbopp mentioned - you don't have to exit the vehicle to use the restroom, get a snack, etc. With a bit of prior planning, you don't need a toad (towed vehicle) if you pick up whatever supplies you might need before you arrive at the RV park; and if you need to visit a place where a small vehicle would be handy, you can always get a rental car. On the other hand, bringing a toad along is pretty simple (once you get past the initial setup costs) and most RV parks offer drive-through sites if you're simply overnighting.
The cost to enter either RV market is probably close. If you have no particular need for a large pickup truck other than camping, then I'd give the nod to the motorhome; and I would lean towards a Class C since the "standard" chassis is easy to get serviced at any truck service center.