Contents of your PATH env var? E:\Perl\bin\ needs to be in there.

You say that the script mapping is configured a certain way, but have you checked to make sure it is defined both for the top level and the server instance below? The top level in the IIS Manager is the machine name. Server instances run under it in the tree display of the Manager and is named 'WWW Server' by default. Perhaps you have the top level script mapping defined, but there is an anomaly in the server instance.

Try perl -V and check to mak sure the @INC paths are right.