I had a '97 E-150 Conversion with a high-top for a while and I liked it for a lot of reasons, but when I was ready to upgrayedd, I specifically went looking for a low-top van to replace it. I can't really give you a feel for the different in mileage as the high-top had the 4.6 and my current van has the 5.4, however, they both get about 14-15 on the highway and towing an extra 4,000lbs doesn't seem to make much difference as long as you're not flogging it.
With the high-top van, there was more room to move around in the back, however, there were also two wooden ledges, one at the front of the van and one at the rear, that I was constantly rendering myself unconscious on. As I'd move from the back of the van to the driver's seat or -- even worse -- if I went from the back of the van to look for something behind the rear seat, more often than not, it seemed, I would crack my head on the wood. I don't know what it is, but you just don't expect that you're going to suddenly loose a foot and a half of headroom.
Speaking of headroom, I'm 6'3" and the high-top was not high-toppy enough for me to stand in the van. It was certainly better than the low-top, but I had no illusions that I'd be able to, say, use the back of the van for work space or anything like that. It was better for changing clothes than the low top is, though, since I could stand up if I crinked my head off to a funny angle.
You do get some extra cubby holes in the high-top that aren't available in the low top van. Since you're storing things overhead, you don't get much space and can't put a ton of weight up there, but I have missed those cubbys on more than one occasion in my current van. Speaking of bearing weight, the high-top is fiberglass, way up high, and not super-duper strong, so using the top of the van for anything isn't really possible. I'm not climbing up on top of mine on a regular basis, or anything, but it is nice to be able to have the option for a roof-top luggage carrier (with 7 people in the van, there is a surprising dearth of cargo space!) or for putting my solar shower on top of the van when camping or racing.
One of the cool things about a high top van is that you'll either have a ladder dedicated to car-wash duty or you'll get to learn all about the local truck washes. I have a couple local car washes that my low top fits in, but the old van needed a trip a couple exits down I-75 to the Walton, KY Truck Wash if I needed to give it a bath.
The biggest problem I had with the high top, though, is that my job has me going all over the place for meetings with customers and a lot of those places are in downtown areas. There are very few parking garages that will accommodate a vehicle that is over 7 foot -- in fact, I have a hard time sometimes with my low top van which needs 6'10" of clearance. In order to park at my office building every day I had to leave the high top van in a parking lot across the street and walk, since it didn't fit in the garage here. The rest of the issues were sort of annoyances, but the parking garage thing is what sealed the deal for me.
Overall, I think as a tow vehicle, a van is a great option and except for Mongo, there is nothing out there with more legroom for a long road trip. It's great with kids since I can open the side door, push all the kids into the van (and out of the parking lot and/or weather), and then worry about getting everyone buckled in or whatever. They are teh suck when it comes time to fill them up with gas, doing the spark plugs reduced me to an incoherent stream of babbling that sounded vaguely like curse words with a side of misogyny just for good measure, and most of the customizers have gone out of business, leaving you high and dry if any of the conversion parts break. My opinion is that if you're looking for something that you need to live with on a daily basis in a city/suburban setting, go for the low top.