The biggest expense after the initial cost of the car rental itself is insurance. Chances are, your personal auto insurance and possibly your credit card, already covers your rental car, although it's worth checking ahead of time for specific coverage.
Denying all add-on insurance policies can save you a bundle. But the one you may want to consider is the loss-damage waiver that relieves you of responsibility from damage like vandalism, theft or flat tires that may occur through no fault of your own. Again, check with your insurance company first to see what rules apply to you.
Opt to return your car with a full tank of gas. Gas stations are almost always in close proximity to rental car lots. Ask at the desk if you're unsure. Even if the rental company offers a lower rate per gallon, you're still pre-paying for a full tank of gas which only pencils out if you return the car on empty. Chances are, you won't.
Considering a GPS unit for your rental? It could add a whopping $15 a day. Use your smart phone for mapping instead.
Now we all want the lowest price possible on our car rental. Consider using Autoslash. Go ahead and make your own booking, then send it to autoslash.com. They will track your reservation and automatically re-book you if they find a lower rate. Frequently, those discounts will come just a week or less before your travel dates. Often rates drop due to the amount of cars left on lot that haven't been rented. You can also make your reservation directly with Autoslash to begin with and they'll offer the same service which is free to you, the customer.