I got told it's better to make things big, then have a larger layout size, things will look better.
Obviously if you have a sprite at 250,250 and on the layout enlarge it, it will effect
The resolution. Shrinking it can be ok.
Also you can set the project to "point" which will give a sharper look to edges
The window size is like a scale out option. Like on text, if you zoom in it will appear larger, but you can set the writing smaller, not sure to what extant you can zoom. And text is limited to 8 (that I've found)
If your making a spore like game, but on one layout, where it zooms out for the next evolution. I would be interested to see how this goes. But youd be better to have difforent layouts for further zooming to cut down on laggingI doubt with 2d graphics it will make much difforence