To do this, open up Automator and create a Print Plugin. For the workflow, you only need to add a single Run Shell Script action with the following line:
lp -d <printer> -o number-up=2 -o media=Letter "$*"
The details of the command will vary depending on your needs. In my case, I wanted 2-up printing to go do my default printer, so I could exclude the -d option.
To see a list of available print queues, type lpstat -a in terminal.
Once you save your Print Plugin, go to the Printopia in System Preferences and add your new plugin as an available destination for printing.
[crarko adds: I admit to being a happy Printopia user, and know there are others around here as well. While not needing this particular item myself, it does suggest some other things to try. Which is why I think it's a useful hint.]