A very strong argument can be made for the Civilization series.
Civilization scratched a 4x itch many didn't even know they had.
CivII improved on Civ's mechanics and graphics, and its expansions added some very user friendly scenario building tools that produced countless quality fan made scenarios. 'Brown Man's Burden' was my favorite, in part for inverting Civ's imperialist outlook. I think I must have gotten at least 1000 hours of enjoyment out of Civ2. It also indirectly spawned Alpha Centauri, which would ruin my argument if it weren't technically a different franchise.
CivIII in added more depth and polish without bungling the spirit of the series. I probably got the least enjoyment out of this one, but only because I loved CivII so much. It is a much tighter game that not withstanding.
CivIV is often considered the deepest of the series, and also was the platform for the Fall from Heaven mods. If you like Civ or the fantasy genre but haven't played it, stop reading this and download Fall from Heaven 2 right now. IMO the best fan mod ever made for any game.
CivV wasn't initially as deep as IV in empire building mechanics, and created some fan consternation in its changes, but it seems internet consensus has come around to it as the most enjoyable and accessible installment, and that hexes and 1 unit per tile have improved (practically created) the tactical element. With the expansions, it arguably eclipses Civ4 in depth or at least comes close. Also, for the first time, it is a pleasure to see and hear rival leaders on the diplomacy screen (if not actually negotiate with them, CivV's only major blemish.)