Mileage can DEFINITELY be gained with any GM full-sized.

Neil make a real good point about the cost of it all though.

A good free flowing exhaust bumped mine up, plug wires, drop in filter, e-fans - they all helped my SS.

Basically anytime you make the motor run more efficiently or get more power to the wheels more efficiently, you'll see gains in MPG.

Some big power adders or cams with lots of overlap will hurt mileage.

I've managed a DIC indicated 21+mpg in my SS in the past. The last two cams I've run hurt mileage a good amount. I hit 17-18 every now and then. I recently calculated my DIC vs mileage divided by gas-pump-readout, and it was within four tenths's of a mpg on that particular tank.