It's difficult picking a single favorite franchise.
On one hand, everyone loves Grand Theft Auto. On the other hand, not *everyone* loves Mass Effect, but it's still pretty loved by tons of people. Then there's the Batman Arkham franchise, Thief franchise, The Witcher, Legacy of Kain, Prince of Persia Sands of Time trilogy, Deux Ex, Assassin's Creed, Gothic franchise, Splinter Cell, Dishonored, Dark Souls, Crysis, Half-Life, STALKER, Bioshock, Dead Space, Metro.
It's hard. I'd say ... The Witcher trilogy is the best franchise for me, followed closely by Mass Effect, Prince of Persia, Thief and Gothic.