Sequence numbers appear to have been originally intended as a mechanism for transaction replacement within the context of multi-party transaction construction, e.g. a micropayment channel.

Yes indeed they were. Satoshis mechanism was more general than micropayment channels and could do HFT between any set of parties.

As it happens, this cannot be made safe in the bitcoin protocol as deployed today, as there is no enforcement of the rule that miners include the most recent transaction in their blocks.

Safe is relative - this is the same logic the original replace-by-fee argument uses. There's no enforcement that miners use any particular ordering of transactions.

As I believe out of all proposed protocols Satoshi's is still the most powerful, I would suggest that any change to the semantics on nSequence be gated by a high bit or something, so the original meaning remains available if/when resource scheduling and update flood damping are implemented. That way people can try it out and if miners are breaking things too frequently by ignoring the chronological ordering people can abandon protocols that rely on it, and if they aren't they can proceed and benefit from the greater flexibility.