The Sprinter normally handles better, but a any of the 24+ Sprinter coaches, especially the full-slide models, may be close to GVWR empty. In this case, an E450 may handle better. Enojoyable to drive is subjective. The E350 is more truck-like, but has way more power, far bigger brakes, and a smarter transmission. The Sprinter is more car-like, and also has a roomier cab.
BTW - those 24+ Sprinter coaches only have 2 seatbelts, because they don't have enough payload for more occupants.
I suggest driving both, and checking the yellow factory weights and CCC sticker on any unit you are interested in.
2000 Ford E450 V10 VAN! 450,000+ miles
2014 ORV really big trailer
2015 Ford Focus ST