I have an interesting twist to this issue I think.  I'm running DNN4.8.1 and my web.config has all the blue lines previously mentioned.  There is one popup control that comes from the AJAX Tool Kit I believe which is generating this missing ScriptResource.axd error.  I get a JavaScript error which says Sys.ScriptLoadFailedException" /ScriptResource.axd? [with some parameter string] could not be loaded.  The odd thing is:

1.  It worked a couple weeks ago

2.  It works fine on one PC running IE6 (control renders and is usable) and on my coder's computer using IE7 and Firefox

3.  Does not work on two of my PCs in IE or Firefox or on my Mac running Firefox or Safari (and I get the javascript error)

4.  It does work in my local testing environment localhost

I'm not sure what the deal is here.