· Choose the direct route.
Google driving directions is your friend (sorry, iOS6 peeps). With it, you can test a few routes to your destination and see estimated drive time as well as view the topology of the area. Skip the route with more mountains, more stop-and-go traffic, and of course more time. If that route is the scenic one you've got your heart set on, then only take it one way instead of round-trip.
· Avoid gassing up near downtown areas, airports and rental car hotspots
$4.73 for an unleaded gallon in downtown quickly can quickly became $4.40 on the way out of a city, which may then shoot down to $4.19 somewhere well down the road. Oftentimes you can't avoid filling up near prime spots, especially if you're renting from an agency that requires you to have a gas receipt from within 10 miles of their rental depot (ah hem Thrifty). The secret to getting around this is to top off at the cheapest place you find, then throw in a few dollars to re-top-off within 10 miles of the depot.
· Rent a manual transmission for improved fuel economy
First you've got to know how to drive a manual versus an automatic car, and double-check to make sure your rental agency has them available. This is no problem if you're renting in Europe, of course, but in America a manual trans is decidedly more scarce. A manual lets you control gears and, if you're doing it right, this will make your manual slightly more efficient than an automatic.
· Consider the rental agency's pre-fill option
This is best for one-way road trips that have you dropping off the car in a city center. Rental agencies will offer a pre-fill option that allows you to turn in your car completely empty and they'll handle the refueling. Ask for the total when you rent the car, and if it's within your budget, it's a solid option that relieves the stress of finding a cheap place at your destination, especially if you're in an unfamiliar city. A recent 3-day rental of our own would have had a $70 pre-fill price, but we declined because, after following all these tips, we only ended up spending $40 on gas ourselves.
· Rent a hybrid or electric car
Your best option is usually a Toyota Prius, Toyota Camry, Honda Civic, the itty-bitty Honda Insight, or the Ford Escape Hybrid SUV. Enterprise has a list of cities that offer electric cars for rent, and Hertz offers an entire "Green Collection" of eco-friendlier car options.