Should be fine, can style any way you like. When it re-arranges the layout for fit, it would stay pixel friendly. Perhaps the scaling for small screens would be undesirable though. In that case you could have different sizes and at certain screen size intervals switch between them. I do breakpoint switching for the first loading screen, I scale the image, but could as well use new images for each step.

I've decided to go for deciding on solutions and then let those solutions limit what type of game can be created. The possibilities are endless so figured this would be a good way to narrow them down :) Game has to work with the visible play area being very different for users, input can only be mouse or touch etc.