For my latest character, I went a little passive-agressive on them. I am playing a thief/mage that has just discovered the joys of vampirism. So at some point I picked Maven's pocket for her house key, I now I use her for my blood fix. I am using a vamp mod that requires you to feed multiple times to return to level 1 (Vampirism Overhaul), so I can feed on her 2-3 times without killing her since she is essential (others you have to be careful not overfeed). So now whenever she makes her snarky comments, I just think to myself, "See you tonight bloodbag..."
Ew, that's gotta taste bad...
Although the only non-hostile NPC I've killed (or sacrificed, I should say) was Lydia, it has crossed my mind whether my game would suffer if the Radiant Raiment snobs disappeared one day. Although they seem to live such pointless, superficial lives I have to concede I like the option of being able to purchase the stuff they sell. Oh well.