If you start having keybinds like ALT + CMD + (F1..F6) you _really_ dont want to have to press an additional FN Keys. I found 4 key shortcuts not viable in the long run if you have to press them multiple times a minute.
With that said:
> So for me personally it's a number of advantages without a single drawback
The objective drawback is the expandability of your shortcuts because you are artificially limited in your options of key combinations. For me that would be a no go. Though I am close to 500 shortcuts in my 3 main applications alone, excluding i3 or KDE globals. I only use a mouse to browse the web.