I am not confident that wheel spoilers/fairings/boattails will make a measurable difference in this case. They would be impractical in any useful size, as a class C is bound to use a lot of suspension travel and get low sometimes, and campgrounds can be very rough.
Completely smooth wheelcovers will also provide an improvement that's difficult to measure, at best. More importantly, if they're REALLY completely smooth they may affect brake cooling, which is especially important in a class C. It may be very easy to put in wheel skirts though, and you could probably even easily do it so they don't look out of place.
All these little things can add up enough to be worthwhile and measurable when you're talking about a 50mpg subcompact, but on this scale I don't think you'll ever notice.
Fairings/boattails for the various stuff sticking off the top could probably help a little. The front of them is generally pretty decent, but the rear is usually not. A measurable difference might even be had from those combined with semi-smooth wheelcovers and the underbody panel. The boattail trailer will be a huge aero improvement but is likely to be a big investment of time and money; I'd recommend it if it's feasible. The part that sticks out over the cab is probably flat-fronted and maybe could use some improving with a fairing.
What model year is it?
Driving style is important, but there's probably not much room for improvement in the way you drive it. You can't start flying around corners. You're probably already using pretty wide throttle openings (because you NEED to just to go). Pulse & Glide probably won't work too well with all that aerodynamic drag, but it's worth a try -- just don't forget what you're driving and pulse to excessively high speeds. You can certainly get away with driving abnormally slow or having big fluctuations in speed, people expect it anyway. If you're a good RV driver and have lots of practice, you probably ALREADY look and plan far ahead and avoid any extra stopping and accelerating, such as by trying to synch with timed traffic lights and getting off the gas as soon as you see a stop in the distance. You probably already need to use engine braking a lot, so if your PCM can do DFCO then it is certainly getting used.
I hate to sound like a downer but it's hard for me to find much room for improvement. I suspect that headers would help, not hinder. I think a custom tune would help, especially with aggressive DFCO and low shift points (and then if you have a "Tow/Haul" button, you could obviously press it when you need more power), and whatever else they do to tune it for additional FE. You could reduce weight as much as possible, but it's tough to get the wife and kids to go along with it. Be sure to empty your waste tanks before driving and don't fill up the fresh water tank unless you do any dry camping. If you've got lots of batteries but don't do any dry camping, remove them. I don't think those weight reductions will help much, but maybe a little.
Hmm...RVs could really benefit from hybrid drivetrains. If it had GM's full size pickup hybrid system with two 80hp electric motors in the transmission, it could have a much smaller gas engine. While the weight on a class C is usually right near design limits for all the components involved, some of the batteries are already there. With aggressive regenerative braking....
For those who aren't familiar with class C RVs, they're the kind that looks like this:
427v8 
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