If you're like me and have both ASP.NET 1.1 and 2.0 on your machine (along with the associated Visual Studio 2003 and 2005 products because you can't help but write software in both environments) you may encounter this issue.  Upon running your website (via http://localhost/xxx or something like that), you may encounter the error page that reports:

Failed to access IIS metabase

If so, you may have installed IIS after installing the .NET framework.  If that's the case, try running to repair your ASP.NET installation and set up all of the appropriate ISAPI extension mappings.

aspnet_regiis -i

If, however, you're like me and had IIS already installed, and you installed VS 2003 and then VS 2005, and then set up a 1.1 virtual directory / website, simply check that the appropriate ASP.NET version is associated with it (Select VDIR --> Properties --> ASP.NET tab).

Edit [ Sept 25, 2009 ]:
I encountered this error again today but this was after I changed my IIS configuration (via machine.config) to not rely on auto-configuration, but rather to use credentials that I specified via the aspnet_setreg utility (I wanted IIS to run under my credentials rather than the MACHINE\ASPNET account).  To fix it, I had to grant my account access to the IIS Metabase:

aspnet_regiis -ga DOMAIN\UserName