John F. Kennedy International Airport: For Midtown, take the AirTrain to Jamaica, then the LIRR to Penn Station or Grand Central Madison: roughly 35–50 minutes, about $20 all-in, and usually the sane choice with luggage. The cheaper AirTrain-to-subway route (A or E via Jamaica/Howard Beach) is roughly 60–90 minutes and about $11–12; use it only if your hotel is close to the relevant line. A taxi can be reasonable for a group, but traffic makes the trip wildly variable.
LaGuardia Airport: Take the Q70 LaGuardia Link bus to Jackson Hts–Roosevelt Av/74 St, then the E, F, M, R or 7 subway. The bus is free; you pay only the subway fare, roughly $3, and should allow 45–70 minutes to Midtown. It is not glamorous, but it beats paying heavily for a cab that may sit on the Grand Central Parkway.
Newark Liberty International Airport: Take AirTrain Newark to Newark Liberty International Airport Station, then NJ Transit to New York Penn Station. Allow about 35–50 minutes and roughly $20–25. Do not confuse Newark Penn Station with New York Penn Station; they are different stations. A car is only worth it for a group, substantial luggage, or an awkward late-night arrival.
Penn Station: This is Manhattan’s main intercity rail arrival: Amtrak, NJ Transit and the Long Island Rail Road converge at 31st–33rd Streets and Seventh Avenue. It is excellent for Midtown, Chelsea, the High Line and the Theater District; use the A/C/E, 1/2/3, or nearby B/D/F/M subway lines rather than taking a cab for a short Manhattan hop.
Grand Central Terminal / Grand Central Madison: Metro-North arrives at Grand Central Terminal; LIRR uses Grand Central Madison below it. You are at 42nd Street and Park Avenue, ideal for Midtown East, the East Side and connections to the 4/5/6/7/S trains. Grand Central is beautiful; it is also a poor place to linger with rolling bags during rush hour.
Port Authority Bus Terminal: Most long-distance and New Jersey buses arrive at 40th–42nd Streets between Eighth and Ninth Avenues. It is functional, not charming. Walk to Times Square, Hell’s Kitchen or Penn Station if close; otherwise use the A/C/E, 1/2/3, N/Q/R/W or 7 rather than queuing for a taxi in theater-district traffic.