I doubt popular relays would sign up to block notes from certain npubs, but first step could be that npubs can express preference not to be mentioned by some other npubs. I don't see why those types of lists would not be welcomed by everyone - if someone is publicly willing to say - I don't want this npub to interact with me, the rest of the network should support that.

Would it be possible to build a limiter like what twitter has where people you dont follow can't reply or otherwise engage with you? If people who are harassed are given control to consent to social interactions as a starting point, that might be worth considering.

Relay-based filtering. Only load comments, replies and mentions from relays that are deemed (by you) to be safe. That should be the default in all clients. What relays are safe? Relays that will require some form of friction for accepting events, and that will actively ban people that have been flagged with kind 1984.