A few of my favorites are U.S. Route 40 in Maryland, US 11 in Virginia, Route 30 (The Lincoln Highway) in Pennsylvania, and the true "mother road" - U.S. 1, which stretches from Maine to the Florida Keys.
There are many others and they are all rapidly changing. The time to explore these places is now, before they disappear entirely.
Route 66, Tucumcari, New Mexico
US 40, Aberdeen, Maryland
U.S. Route 1, Florida Keys
Photos © QR AI/Nightening/MDRails
Cameras: Canon EOS 10D, 5D, 20D respectively. (The Canon 20D remains my favorite.)