All of our applications have Debug="False" in the web.config and Release DLL's.
We have a number of Applications that use ScriptManagers now for .net Ajax implementations. The ScriptManager has a ScriptMode that is set for Release and Debug modes. The default for this is Auto and when it is set to Auto it's value is set based on the Deployment - Retail="True" setting in the Machine.Config.
I have never set this flag on any of our Live Production servers and therefore don't want to just do it!
My questions are:
Setting <deployment retail="true" /> in machine.config is nearly always a good idea for production servers. It'll override certain web.config settings by disallowing:
More good info here on ScottGu's blog: Don’t run production ASP.NET Applications with debug="true" enabled
It's unlikely you'll run into any problems by setting this on your production servers, but check in a QA environment first.