What are the largest cities not built on a waterway in the US?

Fresno, California, population 509,039 (2010 census), is the largest city in the United States that is not on any Interstate highway. Fresno is on the CA-99 freeway, but not on any Interstate.

San Jose, California, population 945,942 (2010 census), is the largest city in the United States that is not on any primary Interstate highway (i.e., numbers 1 to 99). San Jose is on I-280, I-680, and I-880.