Guidance and Setup for 2d Isometric 8-direction Bone-Based Animation?

Wow, that title was a mouthful! So, would love some best-practice guidance as I embark on taking on 2d isometric (8 direction) animation using bone-based skeletal animation.

I have a properly structured and layered PSB for my Player, grouped by each major direction (up, down, sideways, NW, NE, SE, SE) with all body parts separated out as you see here:

Player
-Down
---ArmL
---ArmR
---ForearmL
---ForeArmR
---[etc...]
-Up
---[same parts, etc,]
-Left
[and so on...]

So, for best practices here, I assume I need to set up separate sets bones for each direction (Down, Up, Left, etc.) and put the animator controller at the top "Player" layer so I can control each direction from there, correct?

What else do I need to know to properly set this up for success? What are the tricks to making sure that a controller that controls multiple directions/sets of bones works well and any tips on building my sets of animations (ie, idle animations for each direction, running animations for each direction, etc.)

Do I need to make sure I "disable" each unused layer as I build an animation sequence? For example, when creating a RUN animation for my LEFT character, should I disable each other layer (up, down, etc.) specifically in the first frame of that animation?

Thanks for the help and "perspective" on this! (pun intended, I guess... hah!)