One thing I'd like to try, but have never had the budget for, is completely isolated grid layouts for different sizes. That is, all the layout is in mutually-exclusive media sections. This has a higher up-front cost, but I suspect in the long run, the higher up-front cost would be outweighed by having layouts more fine-tuned for the screen sizes, and more decoupled so you don't have to worry about changes in desktop-size layouts affecting mobile-size layouts.
Flexbox also has a significantly larger browser share than Grid on CanIUse.
Really though, I'm greatly relieved to see browsers start implementing some layout tools that corresponds to how people actually think about layouts. The float years were dark times.