MixTape does it's best to work with your preferred output device. The word preferred is important :)

Have a look at the "General" tab in Preferences:

See here I'm set up to try to use the built-in output as the preview audio and the live stream is going out via an M-Audio Firewire 410. 

MixTape is going to try it's best to use those devices but if the firewire device goes away (is unplugged, for instance) then MixTape will fall back to using the default output device set in System Preferences. However, MixTape remembers that your preferred device was the Firewire 410 and should it become once again available - being hurredly plugged back in for instance - then MixTape will use that again as soon as it can. However if you select a different output device while the Firewire device is unavailable then MixTape will assume that this is the new preferred device and will instead focus it's efforts on sending sound to that.

You can also change the device's sample rate either from "Audio MIDI Setup" or from the manufacturer's supplied interface and MixTape will detect the change in rate and adjust accordingly. Note also that multichannel devices are queried for their preferred stereo channels and these are used where applicable.

We realise there are still problems with some multichannel interfaces and are working to resolve these. If you are affected please email support@atomicdroplet.com with the model number of your interface and we'll see what we can do.