I tried to add a safecontrol to my web.config file and SharePoint crashed (yellow/white asp.net error screen). I undid my changes and saved the file and the error continued. The only way I was able to resolve the issue was to restore the backup I had made of my web.config file.
Further testing showed that making no changes at all but merely saving the file so that the date modified timestamp changes was enough to crash sharepoint. Performing an IIS reset/app pool recycle did not resolve the issue. The only way I've been able to get it back up after any change of any kind to web.config is to restore the original web.config file.
Also, despite my best efforts to turn on CustomErrors in web.config nothing seems to work and the only error message I get from SharePoint is the one telling me that an error has occured, and if I want to see the error to turn off custom errors.
We performed this test in our dev/qa regions without issue, though they are x64 and our production is x86.