Looks like all my Mail.app users are getting the inability to send and receive emails through mail.app after a windows update.
I tracked it down to Event ID: 1309, Event Code 3001.
Exception type: HttpException
Exception message: Request timed out.
I believe that this might be related to MS10-060
Unfortunately, uninstalling this patch got our Mail.app users back up and running.
Need to work on an alternate solution- and MS shouldnt release patches with no known issues.. even when there are issues.