I guess the main difference here is that I am working with Vim and its shortcuts. Thanks to its modes and two leader keys I can use every shortcut using only one modifier.

Only being restricted to usual system-wide shortcuts I think I also would have issues, at least without custom macros. For example I defined macros for Ctrl-Tab and Ctrl-Shift-Tab so I can switch browser tabs more comfortably, but I don't see that as much more than a crutch.