In case nobody is waiting for you at the airport, there are some comfy and not very difficult ways to get down town.
Public transport
The cheapest transfer from Prague airport is by public transport. From Ruzyne Airport take Bus no. 119 and get off on Dejvicka station. Continue by tube (metro) and get off on Malostranska or Staromestska station. You need transfer ticket for 20 CZK.
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 center are just in front of the Arrival Hall. Bus No 119 is most commonly used to get to the center, as it goes to the metro station Dejvicka (green line A), from where you can get to any place from the historical center 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
Minibus
More comfortable is going by Cedaz Minibus which takes you to Namesti Republiky square which is directly in Prague Old town. The price is 120 CZK.
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.
Taxi
The most comfortable, yet expensive way to get wherever you need. The approximate cost of a ride to the center should not cost more than 800 CZK (about 28 EUR). In order to avoid any unpleasant situation that might occur, ude some registered reliable taxi service companies.