Hello Alexis,
You’re probably concerned that the Control room as well as the UR28M both handle some of the same functions - mono, mute, dim etc. The HW controls are independent from the SW controls so actually you can use either - whichever is handiest or appropriate at the moment. (using both together is possible but not especially useful 
)
I usually recommend users to use Mix 1 for the primary Artist Mix. The main reason for this is that a number of things are automatically wired to Mix 1 by default (and can’t be altered). E.g. the Phones 1 are hardwired to Mix 1 whereas the Phones 2 can be switched between all mixes - it follows therefore that phones 2 should be the engineers phones, leaving the phones 1 relegated to the artist cue ergo, mix 1. The 2TR Input is also hardwired to mix 1, making this an ideal Talkback if necessary, without sacrificing a proper input (note this function is then completely independent of the talkback function in the CR - which would typically not be used - set up) this in addition to it’s usual function.
Most important - get it clear in your mind that the mixes and the outputs are two different things and not to be confused. Once you’ve got that firmly implanted, the rest will fall into place.