Gas mileage is probably the least likely reason shoppers look at full-size pickups. The base Ram 1500 can't compete with the most efficient trucks from Ford and GM; its strongest powertrain actually saves more gas.
The EPA breaks down the Ram lineup by powertrain. Base V-6 versions are rated at 14/20 mpg; the engine's aging design isn't up to the task of competing with Ford's newest V-6/six-speed automatic, which is rated at 17/23 mpg.
The Ram's mid-line 4.7-liter V-8 is more competitive in its class. With its five-speed automatic and rear-wheel drive, it's rated at 14/19 mpg. It's also flex-fuel-capable, but when running on E85, economy drops to 9/13 mpg due to ethanol's lower energy content relative to gasoline.
Chrysler's rorty, powerful HEMI V-8 is the powerplant of choice, and its gas-mileage numbers tie its own V-6 for top honors. The 5.7-liter engine earns an EPA rating of 14/20 when it's outfitted with rear-wheel drive; the engine has cylinder deactivation, which cuts off fuel delivery to some cylinders when full power isn't needed. Opting for four-wheel drive, available only on V-8 models, knocks 1-2 mpg off the city and highway ratings for a 13/18 mpg rating with either engine.
The lack of fuel savings with the V-6 makes it a non-starter if you can afford the upgrade to the V-8, and choosing between the HEMI and 4.7-liter is again down to purchase price unless you need and can take advantage of the smaller V-8's E85 capability.