This error normally crops up when you're installing a site on a new PC, or server. It's happened to me 4 or 5 times now and I always seem to forget how I fixed it. When you try and view your site, you see this error:
HTTP Error 500.21 - Internal Server Error Handler "ExtensionlessUrlHandler-Integrated-4.0" has a bad module "ManagedPipelineHandler" in its module list
One way of checking this is definitely an IIS issue, is checking whether your website loads in Visual Studios Cassini. If it does, but it doesn't load in IIS then you will likely need to enable IIS 4.5. Even though you might have installed VS 2015, and enabled IIS in Windows, 4.5 doesn't turn itself on unless you specifically tell it to. Go to 'Control Panel' -> 'Program and Features' -> 'Turn Windows Features On and Off'.
In here, go to 'Internet Information Services' -> World Wide Web Services' -> 'Application Development Features'. Make sure 'ASP.NET 4.5' and '.NET Extensibility 4.5' are enabled.