Returning from a family trip, I will have a
five hour layover in PRG (inbound from KSC lands 7:50am, flight to JFK scheduled for 12:40pm on a Saturday.)

I assume our bags will be checked through to New York and we won't have to worry about them, so will this give us enough time to get out of the airport and see any of Prague or its environs?

What would be the best way to travel,
and when would we have to head back to the airport to make the return flight?

Any tips would be appreciated, especially if anyone's tried this.

Best bet is to take a cab into the city center and then have a nice wander round (such a beautiful city, and the old center is pretty compact). Get a taxi back to the airport, and bear in mind that there are now fixed fees to the airport, so make sure you and the taxi driver both acknowledge this before you get in the car. As a back up, I know that the Marriott hotel has a limo service which is only a few dollars more expensive than a cab. Look for taxis at taxi stands rather than roaming on the streets, and in front of any hotel is a good bet (a small tip to a hotel doorman might also help ensure you get the fixed rate - get the doorman to confirm with the driver). It's not far to the airport from the center, but leave plenty of time, just in case, and make sure you have your connecting boarding passes before you leave the airport for the city!

I know a wonderful taxi driver who twice met my plane in Feburary and drove me to the southern Bohemia town of Pisek where my dad was in hospital. He speaks excellent English, is charming and extremely reliable. His speciality is accomodating airport travelers. Send me an email if you want to get in touch with him. I am sure Mr. Flek will give you a splendid tour. My dad's girlfriend's daughter works for Czech Airlines and found him for me.