I believe I have the SPDIF out correct:

The MOTU 2408 has LED level indicators on the front panel and it is not lighting up at all.

Thanks for pointing that out. I reread the manual and now see I misunderstood how the SPDID options work. I unchecked ADAT1 in SPDIF Out; and checked coaxial in SPDIF In (I am not using it).

Now the level LEDs on the front of MOTU are moving, and the headphone LEDs are lit and there is sound out of the headphones. But no sound (and no LEDs on) for the main output.

Can I assume the problem now lies in MOTU territory (even though there are very few switches when running in DA standalone mode)? Or is there a possibility I missed something else on the RME side?

On the MOTU front panel controls, one can only select the clock source and freq, the ADAT source, and bounce (to shift the channel outs).

On the RME, you say send the correct channels via ADAT. You mean selecting the Main Hardware Out in TotalMix (which is ADAT1&2) and then adjusting the level on Playback ADAT1/2 to establish a route?

Also, on Hardware Out, Assign is set to ADAT1&2.

As you have already hinted at yourself, once you get all the ADAT signals into the MOTU, the rest is happening in MOTU territory, i.e. the configuration of the "Main Hardware Out" and how to route signal there.

Regards
Daniel Fuchs
RME