I noticed this intermittent error with an ASP.NET 2.0 web application about a month ago. I thought I had fixed it when I recycled my application pool in IIS. Since I could not reproduce the error, nor could other users, I closed the reported bug in Bugzilla, and moved on with application development. This bug reared its ugly head again this morning, and my sneaking suspicion about this issue influenced me to investigate further.
The actual error is "Could not load file or assembly 'App_Web_xxxxxxxx, Version=0.0.0.0, Culture=neutral, PublicKeyToken=null' or one of its dependencies. The system cannot find the file specified," where "App_Web_xxxxxxxx" is some random, temporarily generated name, making each error unique. The stack trace containing more details seemed to be filled with red herrings. The errors referenced ASP.NET temporary files, living within the Microsoft.NET/Framework directory. Recycling the app pool, deleting the ASP.NET temporary files, bouncing IIS, and stopping the Indexing Service all seem to help, but only in the short term.
Microsoft recognizes this as an issue and has a hotfix availible to repair the ASP.NET 2.0 framework. They plan to fix this issue in the next service pack for the 2.0 framework, but if you cannot wait until then, give Microsoft a telephone call and have them email you the hotfix. This is was I did, and so far, so good. The errors are gone, and users are happy again.