Route selection can be personal choice.

On some occasions, I've followed a set of maps from adventure cycling or a book such as bicycling the Pacific Coast. I've also followed some established known routes such as the Natchez Trace.

However, most of the time, I let a software mapping program pick an candidate route and then go over the state highway maps to pick more detailed and final routes. I tend to end up on some of the larger state highways. In some states such as Wisconsin, I've found nice back roads and avoid the largest roads. In other states such as Michigan, I've ended up on larger roads. Sometimes when I'm touring, I'll realize the routes I picked weren't the best and/or talking with locals. In those cases, I'll adjust my route along the way to pick some somewhat different roads.

For some specific situations such as crossing the Mississippi, I'll look in more detail at my route candidates and ask in advance (e.g. finding out whether one can cross the Mississippi at Memphis or whether one needs to go further north or south). In other specific situations such as some tours I've done overseas, I'll also read other trip journals to calibrate things.