In MY opinion, the safest hotels (and generally the least expensive) are the ones at Interstate exits away from the larger cities, especially the ones that have a cluster of well-lit businesses at the exit, including truck stops and restaurants. The last place I'll stay is in a large downtown hotel in a larger city - they are more expensive and can be in a sketchy area that you may not be aware of. Also, they are more difficult to get to and leave the next day due to city traffic.

If you have a smartphone, get the hotels.com app to find them and read reviews, you can also get an approximate rate.