One thing I can tell you is every setup is different.
Ask yourself the question why do you have a boat cover. I don't think the first considerations was mpg on the tow vehicle. Mine was to protect the boat and the contents.
I trailer my boat alot, more than I care to, and here are several things to consider.
Depending on how your cover is fitted and the backing (felt) in critical area's it can wear on your boat finish.
I know on my boat and motor cover that fits cleanly my boat, tow vehicle milage is reduced between 1.5 and 2 mpg depending on speed. That being said When I'm traveling several hundred miles at a time I like my cover on, you never know what weather, dirt roads and dust you will run thru, and when making stops there is a little less worry on reach in's.
If I'm going a short distance and confident of weather and road conditions I will leave the cover off. Then you need to make sure all gear is properly stowed so cushions, vest, or what ever items which are not sufficently dense enough to keep them in the boat don't blow out.
Bottom line if you don't use your cover for keeping weather & road out, and gear in whats the purpose. If your cover tears up your boat finish they you have improperly fitting cover. If you want to leave your cover off for improved mileage go for it. If your cover improves your mileage then all the better.
The only time I will leave my cover off on long trips is if the boat has been soaked due to weather and wave conditions on the previous fishing trip and it needs an opportunity to dry out if weather conditions permit.
This all comes down to common sense and what works for you and what is your objective protect the boat and gear, good mileage or both.. Everyone will be different.
good luck GF