I've got 160,000+ miles in 9 years on a '94 E350 RV chassis motorhome, including 9 trips from Oregon to Topeka for the Solo Nationals. It's a 460 with the E4OD. It's been pretty reliable, so far only needing a water pump and a fuel pump, plus replacing the typical 460's snapped exhaust manifold studs. Alignments can be tricky as the front camber changes drastically with/without weight on the hitch, but that may not be as big a problem on the shorter non-RV chassis. Bilstein shocks are a great upgrade and I added a rear sway bar also which was a noticable difference over stock.
Jim