We have the 2005 E350 in our signature - makes a great tow vehicle - very comfortable ride, and will run all day at 65mph - but only get like 9-10 mpg. If you get on some of the Ford Van Forums, the consensus seems to be that the weak link may be the 1000 lb tongue weight limit due to the OEM hitch. There are heavier duty after market hitches with higher ratings available.
We are a little biased, but you might want to look at the bigger Keystone Outbacks. We have a couples oriented Rear Living Room model, but they have several bunkhouse models available. We think the Outbacks are a good value for the buck, and have been very satisfied with ours .....