For those visitng the West Coast...I think for SF and LV, it's pretty easy to get around without a tour guide. Of course, getting to LV would be something, but I'm sure there are coaches that'll bring you there from LA.
LV's not that big, think everything's within walking distance (along the strip). Nothing much to do, unless you gamble...can visit Coke Factory.
As for SF, it's very accessible by public transport, buses and cable cars are easy to navigate. Depending on how much you wanna do, there's the citypass about $40, which would include rides on bus and cable and admissions to I think 5 attractions. Also, from the hotels, you can book tours to Napa valley (if you're interested in wine).
I think LA's the only one that you'd need a car for, so it might be good to get a tour for that and to the Worlds, if you're interested in that. Otherwise, driving up and down CA isn't too difficult (one straight road - abt 8hrs from LA to SF) and you could deviate to Lake Tahoe and Yosemite and Grand Canyon if you like or to the factory outlet at palm springs.
For the East coast, I guess New York would be the place to start, or Florida. Depending on what you like. In New York, there are many tours that you can take in Chinatown, that'll bring you to Washingon DC, Niagara Falls/Toronto, Maine, etc etc. There are also many buses that'll bring you to Boston and other parts along the East Coast that interest you, if you don't wanna drive. Otherwise, driving isn't too difficult either (abt 5hrs to Boston, 40hrs to Florida, 12 hrs to Maine).
Guess it depends on how adventurous you are and how much homework you wanna do. Otherwise, a full package tour also can. For cities like NYC and Boston, you don't need a car to get around, it's easier without a car as parking is very expensive.
Again for these cities, there's the Citypass which you could consider. Check it out online, do a search.
hope this helps.