In case nobody is waiting for you at the airport, there are some comfy and not very difficult ways to get down town.
Taking the bus like any other Prague inhabitant may not be the most comfortable but is definitely the cheapest way to get around.
The stations of the two buses (119 and 100) that will take you to the underground and then to the centre are just in front of the Arrival Hall. Bus No 119 is most commonly used to get to the centre, as it goes to the metro station Dejvicka (green line A), from where you can get to any place from the historical centre in just a few minutes. Bus No 100 takes you to the metro station Zlicin (yellow line B), from where it will take you about 20 extra minutes to get down town. For further info about tickets and timetables see section Public Transport
CEDAZ Minibuses run every 30 minutes from 5:30 to 21:30 from the airport to metro stations Dejvicka (green line A) and Namesti Republiky (yellow line B) and may be in some cases a more comfortable way to travel than the bus, yet less expensive than a taxi. You can find them in front of the Arrivals Terminal, or get information from the info desk at the Arrival hall. A normal ride to one of the metro stations is 120 CZK (5 EUR) per person and luggage but they can take you to any other destination for a fee of 480 CZK (17 EUR) for 1-4 passengers or 960 (33 EUR) for 5-8 passengers.