Fillion, I could buy as a Venkman-esque character. I stress esque, however, because a lot of that character's charm was the Sigourney-ad-libbed line of him seeming like a game show host. He's slick and sleazy, but with the lazy charisma to make up for it. Fillion's too handsome for that.
And while I don't have any problems with female characters in the mix, they'd have to be like Janine. Someone who isn't an obvious sex symbol. Or else, you just wonder why there isn't a ton of sexual tension/frustration going on with her male colleagues.
Or maybe have a female character as the Venkman role, which would be interesting. Someone with a Janeane Garofalo or Sarah Silverman sort of personality, who's in charge of the group. But as I say, if she has sex symbol looks, like Megan Fox, the sexual tension stuff would creep in. A big part of what made the Ghostbusters dynamic work is that they're like a brotherhood. A fraternity. You need a sibling-like feel for the characters and anything along the lines of sexual attraction is going to screw around with that (no pun intended).
The game which came out on PC totally kicked all kinds of ass, though. I fell in love with that thing and the story was great. All the Ivo Shandor stuff, especially and having the original cast voicing it just made the entire thing perfect.