The only rule is they have to be an actual videogame character (no Ariana Grande jokes), and have to be from a series still alive in some form. So, Alis from the OG Phantasy Star would be disqualified as would Joana Dark since they're effectively dead.
If the OP is talking about the entire gaming history, then Jill Valentine is definitely a top 8 as many have mentioned. But if we're taking a picture of the moment? If you consider RE : Revelations a major title, than it's has been 6 years since its release. If not then her last major appearance would have been almost a decade ago.
Hopefully we get R3make soon to change that. Or (hopefully and) RE8 featuring her.
I thought this was a thread about the most interesting female personalities in the industry right now, as in actual human beings and not fictional characters. Like, the thread is cool, but I´m kinda disappointed.