The worst type of bitch, one who is a "mark", which means that he/she is a target that is very vulnerable to attack from others. Like a sitting duck. Calling someone this implies that you intend to murder them or do them harm in some way, or that you suspect someone else will, and that they deserve what's coming to them.
"Biggie Smalls and Jr. Mafia some mark-ass bitches." -2pac ("Hit 'em up")