Well first off on a coast to coast tour my preference would be to use one of the Adventure Cycling Routes or some combination of them. They are nice if they go where you want to go. On our TA we did improvise some sections where we wanted to, but really liked the fact that on the AC part we knew where all of the services and points of interest were on the route. We also liked that we met other cyclists with some regularity.

As far as picking a bunch of cities and linking them... I generally avoid cities most of the time. The AC routes don't usually pass through cities of any size very frequently. When I pick my own route I do the same. The Trans America for example only passes through a few cities of any size. Eugene, Missoula, and Pueblo are the ones I can think of off the top of my head. Many of the towns are tiny, we always considered it a big town if there was a comma in the population (i.e. over 1,000).

If there are no AC routes where I want to go, I like to pick roads that look about right on the map and check sections out with Google Maps Street View. The ones that connect smallish towns and parallel larger roads are often good choices. I don't go out of my way to pick the very lightest traveled roads. In some places I enjoyed the interstate. Out west you are allowed to ride on the shoulder of many of the interstates. I found I-80 to to be kind of unpleasant the short way we were on it, but I-25 in NE New Mexico was delightful (both the access road and the shoulder were pleasant riding).

How much time to allow? A good portion of riders average between 50 and 80 miles per day. Some do more or less, but I think the majority are in that range. That said it is nice to not have a schedule. If possible I like to have a lot more time than it will take. That way you can feel less rushed and enjoy the trip.