Research the best rate for your rental using one of the many travel sites available, but do not book. If you are renting the car directly at the airport after landing, one of the best sites to use is Priceline (see Reference #1). What makes the difference is your ability to see the rates for all available companies, then bid your own price for the car of your choice. The one qualifier for this option is that you must rent and return your car at a major airport to get the special rate. If you will not be using the airport for rental purposes, book your car using the official website for the company of your choice.
Use your major credit card to book the rental for your travel dates. Make sure your primary driver is over age 25 to avoid any additional charges or a mandatory secondary driver add-on. To select the proper car for your needs, research the capacity of the car you are considering. Check both the capacity for passengers and the capacity for luggage, as both are important and may not match from car to car. You don't want to end up with a car that seats four adults comfortably but only holds two suitcases in the boot.
Pick up your car at the airport or other predetermined collection site. Make sure to have your passport, the same credit card you booked the rental with, and driver's license. Inspect the car prior to departure and record any damages so that you are not deemed at fault later on. You will be provided with unlimited miles for travel with the vast majority of car rental companies. Should you not be provided with unlimited miles on site, or should the policy change when picking up the car, decline the rental and take your business elsewhere.
Request an area road map from the rental personnel. They will often have very good maps at no charge, and this will save you $10 at the local bookstore or gas station. Find your bearings and head off, remembering to stay on the proper side of the road! Note the type of fuel that your rental car uses as it may take gasoline or diesel, and getting this wrong can be a major problem. Also note the side of the car where the filler cap is located as this will save you time and hassle at your first fill-up stop.
Return the car earlier than the time you rented it on your return day. In other words, if you rented the car at 10 a.m. on a given day and are returning it 5 days later, make sure to return it before 10 a.m. to avoid an additional day's charge. Make sure to return the car with as much fuel as it had when you rented it. If the fuel level is lower than it was, you will be subject to a fueling surcharge as well as an exorbitant fee per gallon to refuel the car. Drop off the keys and be on your way.