I often run my con games in Sunnydale Elementary - hardly hadr coded with Buffy stuff, but the whole Hellmouth vibe of the place, easy access to antagonists etc. The main problem with using Buffy as an antagonist is that Monsters would probably kick her ass!
The charm of the TV series I think came from the early seasons when the Slayer was a pouty teenager who was incidentally badass and had to fight monsters. There's definite mileage to be gained from winding back the years and having her a lot younger and far more stroppy and temperamental. You can start from a Xander style character who moons after one of the player characters (who no doubt doesn't have any truck with boys), and this unrequited love causing friction with the blossoming buffster.