If you're talking about cars that run on gasoline or diesel fuel, the most efficient car sold in the U.S. for several years now has been the Toyota Prius hybrid. Since 2010, the Prius liftback model has been rated by the EPA at 50 miles per gallon on its combined city and highway test cycle--and the only other cars to equal that are members of what has now become an expanded family of four Prius models.
Several hybrid models from other carmakers are getting closer to Prius numbers, however, with combined ratings of 38 mpg or better. These are often mid-size four-door sedans, including models from Ford, Honda, Hyundai, Kia, and Toyota. Meanwhile, Toyota has said that it is targeted a combined rating of 55 mpg for its next Prius.
Hybrid models are most fuel-efficient in lower-speed traffic, especially stop-and-go urban and suburban uses, when they can travel a high percentage of the time on electric-only power.
But for high-speed highway use and long road trips, cars fitted with modern diesel engines may deliver the best efficiency. It's also worth noting that many diesel-car owners achieve real-world fuel economy that's considerably higher than those cars' EPA ratings--which is rarely the case with gasoline cars.
In the last few years, both plug-in hybrids and fully electric cars have come onto the market, though most of them aren't yet available everywhere in the U.S. (As you might expect, California has the widest array of plug-in models.) The calculations of efficiency for electric cars are measured in what the EPA calls MPGe, or Miles Per Gallon equivalent--a measure of how far a car can travel electrically on the same amount of energy that's contained in 1 gallon of gasoline. The most efficient electric car on the market can travel almost 120 miles on that energy--giving some perspective on just how efficient electric cars can be.
The measurements are more complicated for plug-in hybrids, which can travel from 10 to 40 miles on electricity from their battery packs, and then revert to burning gas like regular hybrid cars until they're plugged in again. The rated electric ranges of these cars vary, but most owners work hard to maximize miles traveled on battery power. Not only is it much cheaper to drive a mile on electricity than on gasoline, but the car is quieter and smoother when doing it.
All vehicles will get steadily more efficient from now until 2025, when the U.S. corporate average fuel economy (CAFE) rating will hit 54.5 mpg. Due to adjustments for real-world conditions, that translates to roughly 42 miles per gallon on the window sticker. In 2025, you can expect every vehicle--from all-electric cars through big luxury sedans to full-size pickup trucks--to be considerably more fuel-efficient than it is today.