Considering sales? Guitar hero. Shit produced more plastic than Down and ExxonMobil in a brief period of the 2000's
Considering importance for the industry?
Definitely Ultima.
Richard Garriot, along with other small series, defined what RPG on a computer is to a point that even Zelda copied it. Then the series laid the groundwork on modern W/CRPG (Ultima 7/8).
And then after almost two decades doing the above... The Garriott invented the MMORPG.
And after all of this... "EA Games Challenge everything bzium!" And the series went to the chopping block.
Given how the genre resurged with Kickstarter and Larian, it's impressive that not a single soul in EA Corporate had the idea to outsource it to Larian.