Had a fifth wheel and F350 dually from 99 to 2003 and really didn't enjoy riding in the truck for running around, so tended to use our bikes and still walk a lot once parked up. Have a Gas 36ft MH since 2003 and still do with no toad, and do a lot of extended trips. Never been a problem except you have to think and research more for a CG on transportation route when getting close to a large city ie; Seattle, LA, San Fran, etc. In all those years have only rented a car for a couple days in Anaheim, and once in Las Vegas at $9 a day to drive out to Pahrump, Hoover Dam etc (book on line and pick up enroute to CG). Drop off on our way out of area again = simple.
With that said and done, we tend to drive a route to visit, see, do something - we don't sit in an area for the sake of just sitting, it's just not who we are. So we stop start in the RV on our travels so being toadless for the most part hasn't caused us any hardship, just like I said extra thought on locating ourselves just outside major cities and on a transportation route.
Try it and you can always change after the fact.