Came across this gem today on a machine that had recently been upgraded to Server 2008:
Error: System error: -2146697191
Turns out that a custom VBScript was sending a form to one of our secure web servers and the certificate chain couldn’t be verified up to the root (even though we bought it from a reputable source). Adding the offending root certificate to the trusted root certificate authorities database fixed the problem.
This does not seem to be documented anywhere on the internet yet, so here it is.