In your early immersion into Grim Dawn you will find yourself overwhelmed with all the mastery skills available when you choose your first class.
I am not even going to address Devotion points here as this is another whole design concept that will actually make you feel like a “Shark in a Paddling Pool” 
You start with the first mastery tree and go WOW, I want all of that, and it gets even worse when you select your second mastery and you want all that as well.
Exactly what I did - I wanted it all.
There is nothing wrong with this. Allocate and open as many of the mastery skills as you can initially, as it will give you a nice feel for what each one can do, and I really DO ENCOURAGE you to do this in your first run through in Grim Dawn. EXPERIMENT as much as possible and see what each skill does and how it affects your build. You will eventually be able to respec the skills later anyway, so nothing is going to be a disaster with whatever you choose.
The problem you will start to encounter is that you almost need the fingering skills of a “virtuoso pianist” and if you then utilize the second quickslot bar, Beethoven’s ability comes to mind.
Like all things in life you cannot have all the cake and eat it ALL!
I have years of play in Grim Dawn since it’s launch with some 70 characters and when going back to revamp some of my earlier builds I too realised that maybe I was also aspiring to be a concert pianist. Too much, too thin and just not efficient.
The other issue with this is that you actually lose a lot of game play visuals as you are so focused on the keyboard with the myriad of key combos that you miss most of the action on the screen, and if fact can end up getting you one-shotted because you did not see the big bad boss launching a killer attack because you were fumbling around with the keyboard.
Once you get a good understanding of the class builds you are looking for, the FEWER keys you need to assign is better. Most builds will focus on just a few aspects of each class and these will be where you will start to max your points and define your bullds key features.
I normally try to limit my offensive / defensive quickslot keys to 1…5 if possible with 3 being the health giver, jumper, special or other main skill you need at fingertip. The toggle skills from items I usually assign to the alternate quickslot so my normal bar is not cluttered. I find this helps in the case of an Arcane mob attack which strips you of ALL your toggle buffs. I jet out of danger and switch to alt quickslot - press 1,2,3,4 etc. to get my buffs back and toggle back to main bar.
With fewer and more effective skills assigned to your bar you will get a lot more visual and interactive enjoyment from the game.
Yes, I know, a lot of the player base are going to say that certain builds will use many of the mastery skills from both classes and are essential to the build and will require adept keyboard skills to utilize their full potential. The caster builds typically require this sort of quickslot assignment range, and they are killer builds if you can “can chew bubblegum, walk and phone text blindfolded at the same time”
I find the easiest is to focus on the 1-2-3 combo keystrokes whollops of my builds prime skills and I can then keep 100% attention to what is happening on screen.
I am not a touch typist or a piano player so I prefer to keep my key interaction as efficient and simple as possible for each of my builds.
To all you multi keyed adepts out there - I do salute you - but my preference is simple good old 123 keys with the skills that count. 
). I trigger all skills with only my thumb, except for auto-attack (LMB or RMB) and certain spammable attacks (scroll down to spam).
it must be very muscular