OBLIGATORY SPOILER WARNING
Hey, there's still two episodes of "Lost" left; still time to blame Kate Austin for all the deaths of the last 6 years... Here's a video rundown of damn near all the deaths on that show; considering some of the most dramatic deaths were either drowning or getting blown up real good, there are a lot more shootings than I thought. And yes, Sayid did a bunch of them, but think of Kate as a potential puppetmaster/mistress and you get my theory... okay, it's just an excuse because so many "Lost" fans don't like the Kate character. Or maybe, after seeing that Jacob/MIB origins episode, we should blame Alison Janney's 'Other Mother' character. Anyway, if the last two shows don't live up to their titles "What They Died For" and "The End", there will be a lot of Losties wanting to kill showrunners Cuse & Lindelof (and considering the resemblance, David Cross had better go into hiding too).
And to think, 6 weeks ago, when I proposed writing an episode about Hurley, I hadn't seen more than half an hour of "Lost"... after three days of watching episodes on Hulu as research, I got TOTALLY HOOKED.

Can't beat River Tam.
Unless it's Dark Phoenix.
Or maybe Lucy from Elfen Lied.
These are probably outside the genres you're thinking of though.

Any genre would do! I didn't list a bunch of kick-ass heroines though because I was filtering it down to the type who go 20-on-1. You of course are free to change the parameters.

Hit Girl, who was the most fun, but the more you think about it the most tragic and disturbing.

Kill Bill, while fun, tried way too hard and was too self-indulgent.

River Tam seemed, IMHO, *puts on flame proof suit* to just be an autistic version of Buffy Summers.

Both Hit Girl and The Bride seemed overly derivative of the less-appealing aspects of some of Frank Miller's work (and HG was also derivative of The Bride, too), and River Tam never really ascended above Walking Plot Device, IMO. Dark Phoenix, on the other hand, ate a star (and wiped out a planet of billions of aliens when the star went nova), and John Byrne and Terry Austin gave her some great axe-crazy expressions, so I second that nomination.