East Coast: New York (JFK, Newark, LaGuardia), Boston (BOS), Philadelphia (PHL), Washington (DCA, IAD), Baltimore (BWI), and Miami (MIA) handle most international and domestic traffic. BWI and Newark often have lower fares.
Midwest & South: Chicago (ORD, MDW), Atlanta (ATL), Dallas (DFW), Houston (IAH), and Detroit (DTW) are major hubs with strong competition and often good deals.
West Coast: Los Angeles (LAX), San Francisco (SFO), Seattle (SEA), and Las Vegas (LAS) are the main gateways. Oakland and San Jose can be cheaper alternatives to SFO; compare all when you search.
The US is huge. If you're visiting more than one region, consider open-jaw or multi-city tickets—fly into one gateway and out of another to save time and sometimes money.