If you fly somewhere and need to rent a car you will typically rent the car at the airport. But the airport location may in some cases be significantly more expensive to rent a car. I've seen this discussed a couple places lately, for example Five Cent Nickel mentions it in their post The Hidden Costs of Renting a Car.
I decided to do a quick check of some prices on Enterprise to see how prices differ by location in the same city.
I checked the airport rate versus non-airport for a weekend rental in my home town over August 14-17. At the airport the cost was $200.99 total and at a non-airport location 6 miles from the airport the cost was $137.84. So that's $63.15 cheaper to rent at the non-airport location.
Then I checked a weekend trip to Vegas for September 25-28. At the airport the cost was $99.56 total and at a non-airport location about 2 miles from the airport it was $166.41. In this case its cheaper to rent at the airport by $66.85.
Saving about $60 bucks on a car rental seems like a good deal but if you're traveling you'll have to get yourself to the non-airport location. That might mean a taxi drive for $10, $20 or more. You should also check if you can rent the car at a cheaper location and then drop it off at the airport on the return for the same fee.
The lesson to be learned here is that you might save a decent amount of money by shopping around for rates at different car rental locations at your travel destination especially for longer trips.