The four major U.S. cities are generally considered to be:

1. New York City - The largest city in the U.S. and a global cultural and economic hub.
2. Los Angeles - The second largest city, known as the epicenter of entertainment.
3. Chicago - The third largest city, noted for its cultural scene, economy, history, and architecture.
4. Houston - The fourth largest city by population, with a significant economy and diverse culture.

These four cities are often recognized as the major cities based on their population size and overall impact in the U.S. and globally.

Some perspectives include Washington, D.C. or San Francisco in the top four for political or technological significance, but population-wise, the largest four remain New York, Los Angeles, Chicago, and Houston.