The most common case for me is commenting on a SO answer something like "This is not what the OP asked about. <They> wanted X and you only talk about Y" and similar - talking in third person about the asker. I have yet to encounter a case where "they" seems inappropriate.

That said, I will not go out of my way to check someone's profile before talking to them. Given a technical aid (e.g. hovercard) that might not be a problem though.