Just a quick simple idea - could you make any “destructive” action (mark all as read specifically, but there may be others) require a confirmation? The iOS interface’s Settings cog and “mark all as read” buttons are awfully close and without a confirmation on the mark all button, well… Bad stuff happens. Not often, but I’ve fat-fingered the settings cog to change sort order and whoops! Everything gets marked as read.
(I’d go as far as saying that shift-A in the web interface should bring up a dialog, because people sometimes don’t realize where their window focus is…)