Here is a scenario that comes up here and there in many communities: you have a topic in which people list different exemplars of a specific type, for example: “books about X”. The main purpose of the topic is to create a list that people can browse and be inspired or whatever. If someone wants to start a discussion about one of these books, that should be a new topic (but, of course, with a link back to the list topic).
In this scenario, it could be very convenient if the reply-to-post button (not the reply to topic button) would default to “Reply as new topic”. I say “could” because it remains to be proven that this actually works rather than creates confusion. But I think it would be worth a try.
My sense is that it would be sufficient to limit this setting to mods and admins via the wrench button in order to avoid any changes in the UI for ordinary users.