Fortunately, the principles of refrigeration were discovered and applied in automobiles! No longer do you and I have to swelter in 110 degree heat. However, running the air conditioner does use slightly more fuel than not running it. Exactly how much depends on several variables that I'll leave you to pinpoint on your own.
So now comes the Big Decision: to run the AC or not run the AC? Some people will argue that it saves fuel to leave it off, but only if you don't open the windows. Winding the windows down, especially at highway speeds, is the surest way to quickly kill your mileage. At low speeds, the opposite happens. Running the AC zaps your mileage, winding windows down doesn't.
But from looking at the title of this post again, you'll see my preference. That's right, I run my AC all the time, whether on the highway or surface streets. Why? Mostly because I can. If I'm driving the car to begin with (vs. riding my bike), I've already made a conscious decision about the transport options on the trip, with comfort sometimes being a deciding factor. On surface streets, 95 degree air wafting through the windows is not comfortable, so I run the AC. Sure, it might lower my mileage a little, but I stay cool and comfortable. In certain situations value arriving at my destination in a timely manner and without being covered in sweat, so I gladly pay the price of gas to achieve that goal.
Some may scoff at my reasoning. Which is fine by me, really. When I drive, I drive my car as a conscious decision, not just because it's what I've always done as natural habit. I commute by bike whenever practical. However, I still have the car for a reason, including AC on hot summer days and nights. So I'd recommend that you do a similar assessment of your car usage each time you prepare to use it. Why are you driving this time? What am I gaining by not walking/biking? If the answers align with your goals and values, then drive. Otherwise, put the keys away and swing a leg over the bike.