Traveling by Air: The San Francisco Bay area is served by three major airports - San Francisco, (SFO), Oakland (OAK) and San Jose (SJC).
The closest is definitely SFO (approx. 30 minutes drive), but OAK isn't that much further away (approx. 45 minutes of drive time as long as you don't arrive during weekday rush hour) and is considered by many to be 'easier.'
We only recommend flying into SJC if you plan to stay in the South Bay/Penninsula area or if you get an unbeatable airfare. The drive to downtown SF from SJC is a approx. 1 hour (non-rush hour).
Traveling by Train: If you are flying into SFO and don't plan to rent a car, you can now take the BART train from the airport right into downtown San Francisco. http://www.bart.gov/index.asp