Hi Michael,
Please uncheck "Show friendly HTTP error messages" in your IE: Tools -> Internet Options -> "Advanced" tab -> "Browsing" section -> "Show friendly HTTP error messages" checkbox.
This will allow you seeing the actual 500 error message that is coming from the ICM.
If you are facing this error in more than one SAP web technology (BSP, Web Dynpro ABAP, ITS services), then I would guess that this might be a configuration issue, maybe involving table HTTPURLLOC (a wild guess).
You can also record a Fiddler trace, which should give you more hints about what is going on in the system.
At last, but not least, maybe you can check the ICM trace file (dev_icm, via ST11 or via SMICM), the system log (SM21) or even the work process trace files (dev_wXX, via ST11).
Kind regards,
Cris