Will a change to the Web.Config file require that I restart IIS

I've run into this exact issue several times, and every time, the solution was to:

1. go to the Control Panel
2. go to the "Windows Components" area
3. remove IIS, let it uninstall
4. reboot
5. re-add IIS (make sure to include the ASP.NET stuff when you check off the boxes).
6. Run: C:\WINDOWS\Microsoft.NET\Framework\v2.0.50727>aspnet_regiis.exe -I

I spent hours debugging this at a client site once, and that was the trick. Since then, every time this has happened, this was the fix.

I'm not sure what the root cause is, but we tore the IIS configuration apart once trying to figure it out, and even had Microsoft RDC'ing into the server in question for 2 or 3 hours, and they couldn't help either.

So I write it off as an undocumented bug in ASP.NET/IIS.

Doing some searches it seems that a lot of times this is because something failed to install properly or permissions get messed up. Check the permissions on your c:\windows\system32 folder (and c:\windows\syswow64 if this is a 64-bit machine).