The answer would probably be a manual and human one: we would have to come to consensus to deliberately flag the accounts used by large holders of non-custodial Hive on behalf of clients and treat them slightly differently, probably around governance and especially DHF voting.
For this sort of thing to bother anyone, the account would need to be pretty giant on a Hive scale and would need to be publicly advertised in some way.
Yeah it often comes back to this but also treating one account differently than another is a huge red flag in itself when it comes to decentralization. Something like this would be very bad optics for anyone outside the system looking in. It also incentivizes exchanges to Sybil attack the network and create thousands of anonymous accounts to circumvent such targeting.
At the end of the day I think we have to get creative with our solutions by employing positive reinforcement strategy instead of negative. Punishing users for doing bad things isn't as effective as rewarding users who do good things (in this case the good thing being having access to private keys).