After weighing the options, I picked up some Ford "facts" along the way (the other whey).
BACKGROUND: I'll brave it here and admit I'm not going 4x4, although I admire and sometimes envy them from a far (a rocky/dusty/muddy far) and I'm not planning on towing much of anything - perhaps a 3,000 pound trailer and object (<300 lb. of tongue weight), but seldom if ever. You could call me conservative.
2010 Ford RB (Single Rear Wheel)
5.4L SEFE V8 330 FFV (nixed diesel on account of cost without need for extra power)
E250 and E350 Super Duty
Axle Ratio 3.73 or 4.10 w/semi-floating rear axle (E24/S24 and E34/S34 which are SMB standard list price options. Ford has a 4.56 axle ratio and full floating options; this increases towing capacity, but not so much cargo carry capacity)
4-speed auto O/D (4R75W) (excluded 5-speed option - 5R110W; a towing thing again)
E250 / E350
GCWR (gross combined weight rating; vehicle w/fully loaded trailer) = 13,000 lb. / same
Rear Axle capacity = 5,520 lb. / 6,340 lb. (PAY CLOSE ATTENTION HERE)
GVWR (gross vehicle weight rating) = 9,000 lb. / 9,500 lb.
UVW (unloaded vehicle weight, sometimes called curb weight) = 6,900 lb. / 7,900 lb.
CCC (cargo carry capacity) = GVWR - UVW = 2,100 lb. / 1,600 lb. (PAY CLOSE ATTENTION HERE)
Payload = GVW - Curb Mass - Occupants = 3,507 lb. / 2,917 lb.
Note: Kurb Weight, Curb Mass, Curb Weight, and UVW terms and thus data can vary (e.g., some calcs include driver and optional equipment, and occupant weight is not a standard figure). The math doesn't exactly add up, but it's close.
After carefully weighing the options, and putting about 2,000 lb. of luxury into the van (including 4 passengers @ 150 lb. ea.), I'm thinking about buying a James Bond passenger seat.
Near as I can tell, the E250 has better milage, lower insurance cost, and lower vehicle registration fees (in WA State), and a wee bit lower overall maintenance and repair cost than the E350. Depending on your driving habits, how much you're pulling, and how many steep hills you climb, the heftier transmission may last longer. Seems like it comes down to a trade-off between towing and carrying (the difference is not how much weight, but whether it is carried or pulled).
There may be a slight difference in the vertical center of gravity too (load height on curb and overall height is about 1" lower on the E350) - important if you're concerned about rolling over, more than how much cargo you can carry. I digress. There's a separate thread about weight and moment, but it lacks sufficient traction for decision making.
P.S. I love this forum.
Really enjoy checking in now and then to see what SMB hard cores have to say.