Mono support could be fairly easily added to ISPConfig - it would just need a couple of lines added to the vhost config in the same way the PHP config is added when selected by the check box.
Here's the following amendments I made to my Fedora Core 4 install to add Mono.
httpd.conf - place anywhere really, I put it just above the ispconfig log statement
AddHandler mono .aspx .ascx .asax .ashx .config .cs .asmx .axd
Vhosts_ispconfig.conf - this data should be added when "ASP.NET" support is chosen when adding a site
I'm sure this could be easily patched in by copying and modifying the PHP sections of the New Site / Edit Site pages