There have long been battles between people investigating A/C vs. use of windows, so let's face it, will we ever find a true solution that always holds true? Perhaps not, but we may get close.
Taken directly from HowStuffWorks.com:
"Based on a study conducted by the Society of Automotive Engineers (SAE), driving with the windows up and the air conditioning on is typically a more fuel-efficient way to drive [source: Hill]. We'll get around to discussing when air conditioning isn't a more efficient option, but let's first take a look at what the SAE found.
The SAE study was conducted at a General Motors wind tunnel and on a desert track. In the wind tunnel, air was forced over the front of the car and also from an angle on the front of the car to simulate a cross wind. In the desert, temperatures and vehicle speed were factored into the study. Two vehicles were used in the test, one was a full size SUV with an 8.1-liter V-8 engine and the other was a full-size sedan equipped with a 4.6-liter V-8 engine. Overall, both studies showed that driving with the windows down has a significant negative effect on the fuel efficiency -- more than using the vehicle's air conditioner.
For the sedan, when the windows were down, the efficiency was reduced by 20 percent, while the SUV fuel efficiency was reduced just 8 percent [source: Hill]. These differences are an important factor in determining just how much the windows down option will affect the fuel efficiency of your vehicle. The study concluded that the more aerodynamic the vehicle, the more drag open windows will create.
When driving at speeds of more than 55 miles per hour (88.5 kilometers per hour) with the windows down, there's a decrease in fuel efficiency of 20 percent or more. Although using the air conditioner decreases fuel efficiency as well, cooling the air through the compressor only decreases the fuel efficiency by about 10 percent [source: Arthur].
So, when traveling at speeds around 50 miles per hour (80.5 kilometers per hour) or faster, air conditioning is usually a better bet, but what about when you're simply cruising around town? Keep reading to find out how you can save a little bit of fuel on those slow-speed short trips."
So HSW says that for faster speeds, A/C is better. Now on to the Chicago Tribune, another credible source:
"The higher the speed, the more wind resistance affects mileage. So, you may be saving gas by driving with the windows open and the AC off at 25 mph. But at 55 mph and faster your vehicle's aerodynamics are increasingly degraded by open windows.
At highway speeds you may get better mileage with the windows up, but it may still not be better than it would be with the AC off.
"Poking around city traffic, aerodynamics doesn't come into the picture very much," said auto air-conditioning guru Ward Atkinson. The auto engineering consultant worked on some of General Motors' first auto AC systems in the mid-1950s. He's a regular speaker on climate control at Society of Automotive Engineers confabs.
While wind resistance from running at highway speeds with your windows down may eat up more gas than running windows-up with the AC on, there is no escaping the fact that "it takes energy to cool a car," Atkinson said."
So the ultimate answer for when is best to use A/C over windows and vice versa? Use that A/C on faster roads or highways, but not while in the city or traffic.
Remember the Mythbusters findings from 2005: "Going less than 50 mph it is more efficient to leave the windows down, but going greater than 50 mph it is more efficient to use the A/C."
» Mythbusters: AC vs. Windows Test with SUVs at 45 MPH
» Primer Magazine: What's Better for Fuel Economy, Windows Down or Air Conditioning?