When you have tons of virtual directories and multiple deployments that has happened on your web-server. The files are compiled and cached under “C:\WINDOWS\Microsoft.NET\Framework\v2.0.50727\Temporary ASP.NET Files\…”
Removing files from the above folder saves a lot of space
They are safe to be removed, below are a couple of blog posts for reference.
And also they explain how we can change the location of the temp folder to a different drive ( I have not done this because by just deleting some temp files I was able to reclaim around 1GB space)
Good fix for multiple site hosting
In your root application, try adding
<location path="." inheritInChildApplications="false" >
around the system.web element.
The subfolder can be a different site.