We are also having this same issue with constant ASP.NET 4.0.x warnings with event ID 1309. We are running the latest Smartermail version 13.3.5535 on Windows Server 2008 R2 Standard 64bit. The server is a new ThinkServer and is dedicated to Smartermail.
This issue seems to cause the Smartermail service to stop suddenly requiring a manual restart. We've also had a few random reboots with errors on the Smartermail service causing this. I've never seen this until we upgraded to 13.x.
Any help to get these bugs fixed would be great.