Any of a dozen mapping programs will give you alternative routes.
What is your reason for avoiding major cities and what do you consider a "major" city?
If you just like to travel back roads, have at it.
If you are worried about heavy traffic, it will usually be easier to go thru the major cities but time it to avoid rush hour. There are exceptions but my experience with traffic data collection is 10am-noon is typically the lowest volume time during the day (late night is better if you don't mind traveling then).
I just plugged it into Google Earth and for a very long route, only major cities were Denver and Dallas (texas).
- In terms of traffic, Denver is more marginal as a major city but there isn't a good quick bypass.
- Dallas, you could cut across to the north to I-30 and then down I-49 but really probably more hassle than just running thru the city off peak.