DrewMelton one thing to think about is support of point sampling. It requires WebGL (so no <IE11 and mobile Safari) and I've noticed it has a big impact on performance on (some?) Android devices using CocoonJS.
I posted a little bit about it here: 24h GameHack - 'Beyond the Wardrobe' - GameStick!
Fortunately I found out that you could just batch resize images in the project directory to a higher resolution (using nearest neighbour image interpolation in Photoshop), and all assets (except spritefonts and tiled backgrounds if you use them) retained their stage size, and I was able to disable point sampling for a comparably crisp effect.
So I'd personally recommend working on the small scale, then if you find you're having issues with point sampling, you can always batch resize your assets and switch to linear sampling.