If you are daft enough to remove your HttpHandler from the GAC don’t be surprised if sharepoint goes bang.

I did just that and hit Site Settings and got a plain file not found message, not very helpful.

I narrowed it down to the last scarey thing I did which was HttpHandlers, deleted the entries and all was working I then figured I removed it from the GAC and sps bin folder so Sharepoint was not finding the dll.  Pretty poor message though.