Book flights as early as possible - at least two months in advance.
Book flights on a Tuesday or Wednesday - the airlines seem to raise their prices for the weekend (Friday-Monday).
Use Kayak.com for flights - you can always check it against the airline's own website.
Use Expedia.com for city break packages - it's more often cheaper and a huge time saver.
Airlines charge for checked-in luggage so remember to a carry-on sized bag of no more than 45 inches (total of length, width, depth) and no toiletries that exceed 100ml. A trip to Target will sort you out.
Accommodation.
Look for subway/metro links near to where you intend to stay - even if you're traveling by car, you might find it's cheaper and less hassle to park the car at your motel and get public transport into and around the city rather than sit in rush hour traffic and pay extortionate parking fees.
Motel6.com is a good guide price for how cheap you can find a motel in that area - you won't find a motel more than $5 cheaper than the Motel 6 price (but you might find more for your money).
Use Hotels.com for the 'stay 10 nights get 1 night free' offer but don't forget to compare them to Expedia.com and/or Kayak.com.
Book accommodation early - especially in peak season. But if you're traveling during the winter months you've probably got more flexibility to negotiate rates.
If you haven't booked accommodation for that night, use your TomTom GPS to find motels/hotels along the route and start calling them from your phone. Most places have internet so take a laptop if you can and book your future night's accommodation in advance.
You might think hostels are the cheapest form of accommodation but splitting the cost of a motel between 2 - 4 people will be as cheap or cheaper + you get your own TV and bathroom!
Car hire.
Use Google maps to plan routes and determine times between places.
Invest in GPS before you go because car rental companies will charge you $8-15 per day. Moreover their GPS can be a nightmare (I'm looking at you Hertz NeverLost!) so buy a refurbished TomTom from Amazon.com for $70.
Rent an economy/compact car for 2-3 people, a mid-size for 3-4, and a full size for 4-5 people. You will get miles more out of the smaller cars than the larger ones. An economy car will only cost $35 to fill the tank and can get you up to 8 hours of solid driving time.
If you're not over 25, try to find yourself a driver who is! Most car companies will insure drivers under the age of 25 but it'll cost around $20 per day extra.
The absolutely essential insurance not to leave without is the 'collision damage waiver', which will exclude your liability for any bumps and scratches.
Don't prepay for a tank of fuel - it's only slightly more convenient and you'll seldom bring it back on empty thereby wasting money. Instead agree to bring it back on full - you'll just need to stop at the gas station nearby before you return the car (another good reason to invest in a GPS).
Alamo.com is your guide for car rental prices and we always had a really good experience with them.
It's good being a foreginer as you'll get a price that includes all the insurances and unlimited mileage.
CarHire3000.com generally offers the cheapest car rental but be aware that it'll be non-cancelable and usually come on the condition that you commit to prepaying for fuel (wasting money).
If you're booking a flight/hotel/car package from Expedia.com, always see the price without car hire because it's more than likely you can save a significant amount of money by booking this part separately.
Car rental companies charge between $250 and $1000 to drop a car at a different location so bear this in mind when planning your road trip. For this reason, all but one of my trips were a loop from the airport to the airport.
Miscellaneous.
Find out all the costs and over-budget to avoid arguments later on.
Buy a good water bottle and fill it up everywhere you go - every major tourist attraction has water fountains. And while you can't take liquid through airport security, you can take the empty bottle and fill it up on the other side. This is easy, convenient, healthy and free!
Travel as often as you can during the winter months (October-May) as flights and accommodation are so much cheaper - the cost of some accommodation is quadrupled in the summer!
America has an unhealthy obsession with coupons but go with it - search the internet for whatever you want to see or do and/or the company name + the words 'coupon' 'code' 'discount' etc and you'll often find ways to get money off. This is another good reason to take a laptop with you.
If you're used to the idea of tipping for excellent, over-and-above service, think again in America. Tipping is pretty much conditional here and the guide price is 10%-15% on something where you receive a service i.e. being waited on in a restaurant.
Taxes are another issue if you're used to seeing only the price you pay. Taxes are added to most things and they vary from state to state (6-12%) so it's best to have a mental guide of 10% for this too.
If you're going to be in the US for a considerable amount of time, buy yourself a cheap mobile phone - you can pick up a basic Nokia handset and $15 credit on AT&T pay-as-you-go for $35.
And if you can think of any other tips, or disagree with mine, please do contact me.