I only use Comodo for the firewall and keep defense plus disabled. I WAS having the same trouble with supreme commander not loading. I found a solution besides uninstalling completely, and as i dont use defense plus anyway, this is perfect for me. You can set a "disable defense plus permantly option", which requires a reboot. Under Comodo, hit the defense plus button in top right, then advanced on the left. Then hit the defense+ settings option on the right section. Under the default tab, general settings, you will see a check box at the bottom for disabled defense+ permantly. Then you reboot when prompted and you are good to go!
this was found by a very helpful newbie on the SupCom forums by the name of MajmX.
aparantly another SupCom player solved this recently, and considering that both SupCom and Demigod both have a common heritage in the Moho Engine i expect this will also work for Demigod.
[BTW:] my computer is called OMGSplosion, and no; Comodo DF + Moho does not make my computer.