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I'm running 14 on Windows Server 2012 and IIS 8
My SSL Cert was expiring, so I renewed and installed the new cert, then updated the bindings in the admin. Afterwards, I could not access the website, either locally or on remote computers. SMTP, POP, IMAP worked fine, however.
Eventually, I follwed the instructions on https://portal.smartertools.com/kb/a2903/system_net_sockets_socketexception-no-connection-could-be-made-because-target-machine.aspx
Changing MailServiceAddress to IPC fixed the problem. However, I was wondering why this happened, and how I can avoid it in the future. Apparently, every time I upgrade I'll have to remember to change the config file.