I've been pleased with the Ford chassis, and I'm a long time Mopar guy. Just be prepared for 7-8 mpg and no more on the E450 (doesn't seem to change whether I'm towing or not), maybe a little better on the E350 with a shorter coach body.
The only real regrets I have with our current motor home is the lack of outside storage. We manage to make do, but I have nowhere to lock up my extra generator (we don't like running the built-in Onan in quiet campgrounds). Everything else I've been able to mod or live with.
We spent about six months looking at fifth wheel floor plans before buying, and there were no regrets when we had it. Had we spent more time looking at motor homes, we might have eventually found one with more storage. But we were also looking at the used market, and that didn't leave a lot of time to shop.
Don't be afraid to look on the used market, either. We've done well, and got more coach than we could have new. I'm also less afraid to do mods to it... ;)