This sounds a lot like the question asked and answered in http://www.digi.com/support/forum/44034/how-do-i-get-realport-working-on-connectport-x2d, however when I followed that procedure it did not fix the problem.
I have a Digi Connect ME and a ConnectPort X2d. I set up a RealPort for each, in exactly the same way. My serial terminal connects fine to the DiGi Connect ME virtual COM port, however trying to connect to the VCP of the ConnectPort X2D yields the error "Unable to open connection to COM2. Unable to open serial port".
I have enabled the serial access to the gateway radio in the ConnectPort X2D (per the above link) but it makes no difference.
What am I missing?