Jamie Jensen's "Road Trip USA" guides one through a collection of trips on the Numbered U.S. Highway system that yet exists intact in the middle part of the country where everything was not blanketed by superhighways. The edition I have covers six North-South trips, four East-West trips, in addition to Route 66, which was one of the diagonals.
US-60 (I've traveled eastern New Mexico to the Atlantic Coast) will connect you with Kentucky through southern Missouri (crossing 66 in NE Oklahoma). US-412 will connect you with Tennessee (crossing 66 in Tulsa).
Because of my destinations, I more often follow diagonal routes (US-24, US-36, US-54, US-98) than the old E-W (US-2, 20, 30, 40, 50, 60, 70, 80, 90). Actually, most of those highways still exist, but the current US- number route signs will have you follow Interstates instead. The historic routes of those highways are now more often state highways.
Many of the Interstates were put on new alignments to bypass, by at least a few miles, the towns and small cities the old highways served. Interstates got routed through only major cities to serve as expressways for the cities that did not yet have them.
Most of my interest in following the old highways is to see the small towns.