With a F-150, is it smart to drive with the overdrive on? Will it give me more power? What about gas?

Try to think of it this way. As a kid, did you ever ride a bike generically called an English Racer? It normally had three gears with a small shift lever on the handle bars. The three gears (different size sprockettes) were attached to the rear hub of the rim. After getting the bike moving, shifting the gears just placed the chain in a different sprocket on the rear wheel, thus changing the ratio of how many turns of your foot resulted more turns of the rear wheel, resulting in less leg effort on your part. New Ford PU's have six gears in the tranny. When on the highway, and in sixth gear, the rpm drop resulting is less gas used because it does not take as much effort to keep the several ton monster moving.