No problemo, lets take your sprinter for example.
Lets say you drive 5000 miles per year.
And you said you get around 21-24mpgs, right?
I have NO idea what diesel costs right now, but lets call it $4.00 on average in your area.
So 5000 (total estimated miles) divided by 21 mpgs (estimated worst economy) = total number of gallons you'll need to drive that mileage (238 gallons)
So take 238 and multiply it by the average fuel cost ($4.00) and you should get a rough estimate of what your annual fuel cost will be: $938.00
We can do that with the E350, too.
5000 miles divided by 8.5mpgs = 588 gallons
588 gallons times $3.75(estimated gas cost) =
$2205 annual fuel cost
As you can see, your fuel cost more than doubled with the 4x4 van, but here's the thing. E350 v10's are very reliable, very common, and that van packs a TON of utility into a very small, nimble package. If you CAN budget for that fuel cost each year, and are not suprised by it, and the van fits your needs/wants, I think you'll find a very low amount of regret when paying for fuel no matter which one you choose.
That's one thing I had to come to terms with when having a family size larger than 4. For us to be comfortable, it simply puts us into a bigger vehicle category. I LOVE 1st gen 4runners and generally smaller rigs with their accompanying economy, but we simply don't fit.