Speed does make a huge difference, given that the biggest factor in towing a travel trailer or 5'er is wind resistance. We track every tank meticulously. Our best ever was towing on a calm night across eastern Oregon state highways, where the speed limit is only 55. Cruise set at 55 mph, we got just under 13 for that tank. Another tank trying to meet an appointment, had us going 75+ into the wind. You couldn't tell the truck was working any harder than usual, but it showed at the pump -- 8.2 mpg for that tank!
Note -- this was on our '06 Duramax diesel.