Sounds good :) I always get stuck on design too, lol.
Maybe a bit offtopic from this sub, but why do you refuse to use out of the box frameworks?
Also, in regards to css framework, have a look at https://tailwindcss.com/ - provides many utilities for grids, colors etc. I think this would be perfect for a game.
Ah, sorry, I assumed too much!
It depends a bit on your game. What's the minimum set of features you'd be happy with before calling a prototype functional?
For a general recommendation, I've found vue.js to be enjoyable. It's a bit to get your head around at first but can save a ton of time as your app evolves. There are video tutorials at vuecasts.com which are ran by the same guy who runs great video tutorials at Laracasts for the Laravel PHP framework.
Also, Twitter Bootstrap is good to lean on if you don't mind the generic style. That will also save lots of time, and you can always modify it later as needed.
check out Endless Sky too if you haven't - open source community of modders doing a pure EV revamp one Github pull at a time. (well, the engine was written by one guy I believe, but massive content from the community)
https://endless-sky.github.io/
It was seeing that community that pushed me over the edge to give this craziness a go.