Depending on the part of the US, public transportation can vary from widely available but somewhat time consuming to locally not available at all. This is an important consideration because without planning for it your trip to, for example, Oklahoma, Texas and Louisiana might be less than anticipated.
While there are services such as Greyhound bus lines and some smaller lines that run throughout the country, there are equally some areas best accessible by hired car.
When hiring a car, often available in the airport you fly in to (booking online can save you money) look the car over thoroughly and remember once you sign any scratches or imperfections not listed on the page you are liable for. Greatly advised: insurance. This protects you in the event of an accident as well as incidental door damage or other problems that can occur in day to day travel. While it will add to the cost of your trip, if there is a problem it can save you thousands of dollars in fees.
That said, the Green Tortoise has an extensive bus travel network that focuses on major destinations and travellers from around the world. These offer organized tours that, for example, can take to to spectacular sites such as the Grand Tetons, Yellowstone Park, the Badlands, the Great Plains, Chicago and Niagra Falls - a 14 day cross country trip that is sure to be memorable for those enjoying the natural destinations. Cost for that particular trip on their site is $609 plus $181 for food/parks. Bring your camera and lots of batteries for digital cameras and film for those that need it! These bus trips are very different from the Greyhound line.
Still other Green Tortoise trips venture from the US down into Mexico. Trips can be as little as four days (New York City) or as much as nearly a month, with most being 7-14 days. There is also one way trips from Los Angeles to San Francisco for $39. The disadvantage - you're on their time frame. There are certain dates that these trips are available. The advantage - it's designed for backpackers! The cost is reasonable, you have your itinerary set and don't have to drive. There is somewhat a safety factor also.