I think mine has to be the Sonic series from Sega Genesis. I found out a few days ago that there's a Sonic 4 downloadable game in the PS3 store. Now I'm stoked to buy it. Haha
When I was a kid, the Sonic the Hedgehog games had to be the best games I played in the '90s. When the "Sonic Mega Collections" was released for GameCube a few years ago, I didn't mind pitching out the $40+ for it brand new.
Other series worth mentioning:
- GTA (probably tied for #1 best series imo)
- Gran Turismo
- inFamous 1 & 2
There are others, such as Assassin's Creed, that I would have mentioned but I haven't played them much, so I can't really vouch for how great they are (though I will admit the AC series is pretty bad ass).
I have the most history with RE, but I was a bit disappointed with the last one, and they've had some filler games in there that were really disappointing. Uncharted could jump if this third one is as good as it looks, or even just as good as the last one really. GTA is still a social event for me in my mid thirties. I have a couple buddies who are gamers, and it remains the only game really that we all get and talk about. They are so long though they almost become like work finishing them. IV I remember coming home after work and not looking forward to the thought of needing to put a few hours in to make some headway.