Inarguably GTA. No other game series comes close to the cultural depth. I can't think of any other realistic contendor. Shallow kids games (mario,zelda,pokemon) don't count as they are a dime a dozen and not indicative of the quality and production values a videogame can aspire to. Half-life has only had 2 releases and linear fps are not anything special. What other series with as many releases has been as high quality? There's nothing. But you'll all disagree and just list your favourite game series instead.
There's still nothing else out there like the GTA games, other than maybe RDR & LA Noire. All other openworld/city/sandbox games are mindless fun and don't have the attention to detail or depth GTA has. Infamous,prototype,etc. they don't have radio stations, they have hardly any characters, they have simplistic plots and missions and focus more on mindless gameplay. Nothing comes close to GTA in characters, writing or setting. The whole series is a great social commentary relic of american culture in the past 100 years. Different eras and different cities represented in the music, the fashion, the ethnic groups, the cars, architecture, and tone etc. People don't appreciate enough how much more work and detail is put into GTA than any other game series.