This error occurs mostly on Server 2008 R2 systems where .NET has become corrupted. You may see errors such as

• HTTP Error 500 - Internal Server Error Handler
• HTTP Error 500.21 - Internal Server Error Handler "PageHandlerFactory-Integrated" has a bad module "ManagedPipelineHandler" in its module list.

Fortunetely, it is an easy fix. Follow the steps below on the smartImager server:

1. Log in as an administrator to the smartImager Server
2. Open an elevated command prompt
3. Change directory to the folder where .NET is installed. By default it is c:WindowsMicrosoft.NETFramework64v4.0.30319SetupCache
   • Note: If setup.exe is missing from the above directory, you may need to change into a sub directory such as v4.5.51209
4. Run the command setup.exe /repair /x86 /x64 /ia64 /norestart
5. At the new window popup, select Repair and click Next
   • Note: Repair will take about 5 minutes. You may see a popup about another installation running, simply wait a minute and click Retry
6. After repair, switch back to the elevated command prompt and type in iisreset

You can now launch the smartImager web console without error.

Reference: https://msdn.microsoft.com/en-us/library/hh168535(v=nav.90).aspx