If I can reach them (email in their profile or in their comment) and they ask a question I try to reply via email. Sometimes they offer suggestions to me or leave some type of comment I want to reply to and again, if I can contact them by email I do.
I don't reply to every single one though, just no time. I don't respond to comments by leaving another one because I don't think the majority of people follow along the comments for the most part - I think they just leave a comment and maybe skim the others and then forget about that post or at least the comments.
I do probably 90% of the time...even during giveaways. I just think its really important. I use a handy plugin called "Comment Email Responder" on some...it leaves a comment and sends an email back to the person Im responding to simultaneously.