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When I had my S10 (short bed, regular cab, 2wd), I found I did the best with the tonneau cover on. No tonneau with the tailgate up cost me a few mpg. I never drove enough with the tailgate down or off to ever really quantify the effect of that.
Odds are, unless you have a really odd truck (and the original poster does not), you can probably find a cheap used tonneau, or even make one.
On the other hand, if you do lot of city driving, no tailgate would probably be best, as those things are right heavy.
An aero cap would be best (...if retaining the truckiness of the truck is important), of course, as they approximate a Kammback.
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