Remember, it’s only pixel art because the required dimensions are so small. But you are not held to any aesthetic guides. If you can make it work in the space you are given, then go right ahead!
ZOOM OUT! It’s easy to get into the details, working zoomed in much closer than the final size. Make sure to constantly be looking at the artwork actual size to check and double check readability.
Keep color in mind: Use color/saturation to communicate with the player. Maybe you keep danger consistent (i.e. always red?). Keep ground/foreground elements brighter, purer than background? Make important elements stand out - try making it obvious that a collectable can in fact be collected, while a background element can’t.
Use layers! Instead of trying meticulously color pixel by pixel, draw a shape with local color and basic detail. Then make a new layer above the main sprite, mask off the sprite shape, and draw in the darks. Multiply, overlay, color burn to affect all local color below. Do the same for the lights. This way you can achieve a look with lots of depth and detail, and still maintain pixel perfect accuracy and not have to hunt and peck through the color palette a million times.
REPEAT! If you’re making a dirt texture, draw one tile of dirt. Then copy it and rotate it by 90°. Then copy it again and redraw a few of the lines. Then copy it and change some of the color. Don’t make more work than you have to. This is especially helpful for repeating textures like water, grass, dirt, etc. It allows you to make a large grouping of texture fast, without getting that cloned pattern look of just repeating the exact same tile 10 times.
Another way to add variety is to just draw one tile, repeat it as many times as needed, then draw on top of the entire area, adding details and variation that hide the repeat.
When you’re working in a small format, pixels matter. To make sure you work as crisply as possible, here’s a few tips:
Use the Pencil tool, not the Brush tool. In Photoshop the pencil tool is located in a fly-out menu under the Brush tool, the Pencil tool draws in perfect pixels.
Turn Anti-Aliasing off. On everything! By default Photoshop wants to smooth out your edges to make things look nice and blended. But at such a low resolution, this equates to looking muddy. So when using a tool like the lasso, wand or polygonal lasso tool, make sure to have the anti-aliasing checkbox ticked ‘off’.
Once you’ve drawn an item, only rotate it by 90°, 180°, or 270°. This maintains pixel integrity. If you try to rotate your object (other than in 90° increments), Photoshop will try to extrapolate the pixels and create a fuzzy line or a wonky edge.