We have a 75 gallon fresh water tank and usually run with it full or pretty near full. Fully loaded with our Honda Odyssey in tow, we're near 25,500 lbs. gross combined weight. Carrying only about 10 gallons of water would drop our weight down to about 25,000 lbs., about 2%. It's just not going to make a difference. At highway speeds, wind resistance is more of a predominant factor in mpg than the weight.
I'd rather have the water and not need it, then need it and not have it. :) Plus, our water here at home is oftentimes much better than what we get in other areas, so in those instances, it's nice to have our own.
~Rick