If we don´t want to take public transport, taxi or have no pick up from airport, we like to use Airport Express (AE) - airport shuttle bus going directly from airport (Terminal 1 and Terminal 2) downtown to Main Train station located literally a stone throw from Wenceslas sq. (city center). And of course you can use the other direction as well:)
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It is a convenient and affordable compromise between taxi and public transport and cost only 60 CZK / person. AE buses are running every 30 minutes from / to airport and it is a direct connection. The whole ride (with no traffic) can take aprox. 35 minutes maximum. In operation from 6:30AM - 10PM.
During the day (afternoon peak) you should count with some extra time spent on the bus as it can get stuck in traffic jam:(