I'm all for the systemic approach, which means putting the boundaries inside the limitations of the rules: you should be free to ATTEMPT to kill anyone. Which doesn't mean you are also entitle to the right of having a fair chance to succeed.
I'd be perfectly fine with certain fights being virtually impossible for the players and their parties.
If you attack citizens on the streets, law enforcers should spawn and kick your ass. If you attempt to murder a high caliber/powerful NPCS, they should be well protected, by their own set of abilities, by over-leveling your party and by having bodyguards, etc.
