but in the real world you die almost instantly if your throat is cut.
I just want to say that you only die almost instantly if the back of your neck is cut, which is where the spinal cord is, having the front of your throat slit is actually a long and painful process of drowning to death on your own blood.
to answer your question, putting a knife to someone's throat is equivalent to the "Put At Weapon's Point" maneuver, which levies a -150 penalty to defense. Surprise would be another -90, but realistically speaking, someone who is helpless against an attack (i.e. sleeping, completely paralyzed, etc) is at -200 to defend themselves, so I would not stack those two penalties to -240, but only up to -200. Whether you are doing this from behind or the front matters not, because as I've already stated the penalty can't logically get worse than -200, however, if you don't have surprise, doing it from behind (-80) would stack with the -150 to -200, so it's in your best interest to do it from behind anyway.
Then striking a vulnerable point causes an automatic critical, unless they've got a really good physical resistance, chances are you'll hit the "targeted location is destroyed" critical level, which, immediately destroying a vulnerable point causes instant death.