I'm skeptical of infinite nesting. It does help in some cases, but disrupts the vast bulk of threads visually and adds a complicating decision to replying. Longer chains with branching are horrible to navigate, and the replies get shifted ever rightwards. This puts a limit on the effective number of replies (even if you subthread it like lesswrong, having to click through is clunky inconvenience), which is much worse than the problems caused by lack of nesting imo.
You can gain much of the advantage of infinite nesting without any of the major costs by creating a "reply in new thread" option for those cases where it really is important to reply to different parts of a post separately, which creates a post linking to the new thread.
Having strong norms of "one topic per top level comment" (possibly mod-action splitting posts for a while, or having a way to give feedback suggesting it easily) would also reduce the need for heavy nesting, and organize discussion more neatly.