Best connection Mac Mini to Denafrips Pontus II

One thing you could do would be to add a Denafrips Iris now to clean the signal from the Mini and run i2S into the Pontus, which also helps, and then add a better streamer later that you definitely wanna do.  Or you could get a better streamer now and add an Iris later for a nice performance bump down the road (I did this).  Option 1 costs less now if budget is an issue, but the bigger improvement will likely come from a better streamer.  Here are an Innuos Iris and Zen that if you can swing just get both now and be done with it — the performance improvement will be substantial.  Just one idea FWIW, and best of luck. 

https://www.usaudiomart.com/details/650268513-denafrips-iris-ddc/

https://www.usaudiomart.com/details/650246960-innuos-zen-mk3-4tb-storage/

What @soix said

The USB out from the Mac Mini will ultimately disappoint.  Seriously consider investing in an I2S renderer, like the Pi2AES Mercury.

+2 what soix said. 

I have the Venus. My understanding (and I could definately be wrong), I2S uses the source clock, but usb relies on the DAC clock (in this case your Denafrips). So, you should choose the stronger of the two....I suppose in your case it's your Denafrips: therefore use a usb connection. I have the Venus 15 and I use usb coming from my Eversolo streamer - sounds awesome! This reviewer discusses that here :

iiWi Review