My only problem with Big Sister encounters was you(or at least I) could never tell where she was coming from. Here's an example:
In the bits right after The "Amusment" Park part, I was out of eve hypo's, health kits, money, and most ammo for everything but the Shotgun(coincidentally my favorite weapon) because I spent time letting a Little Sister gather ADAM.
I rescue her, and hear that framiliar cry. Turn around, get shot, wake up in a Vita-chamber.
Get out of the Vita-chamber, Hear Cry, Prepare myself by franticly laying Trap Rivets and preparing my Fist O' Lightning[small]tm[/small]. She comes up behind me, Wake up in Vita-Chamber again.
Get out, hear cry, run into a store. "Surely," I say to myself, "I'll be able to see her and Fist O' Lightning[small]tm[/small] her before she gets me now!"
Needless to say, I wake up in the same Vita-Chamber.
I think about staying there, until a roving Splicer decides it'll be smart to pump lead into the chamber(I didn't know they could do that at the time..) get out, hear cry, introduce splicer's face to Mr. Pointy Drill[small]tm[/small], and getting REALLY tired of fighting her, I head straight toward my objective, only for her to pop out of literally nowhere and shoot me again.
I decide to get out of the Vita-Chamber one more time before turning off the console. Hear Cry, wait, hear ANOTHER cry, go to investigate, see Sister has been hit and killed by Rocket Turret.
That is one of the most frustrating gaming experiences i've ever experienced in a game that wasn't horribly broken, topped only by Airman's stage in Megaman 2.