Aseprite
Aseprite combines pixel-precise drawing, layers and frames, tags, palettes, onion skinning, and sprite-sheet export in a focused workflow.
Why use it
Its specialized pixel-animation operations remove a great deal of repetitive setup from characters, effects, and tile production.
Where it fits
Use art, animation, audio, levels, and narrative to make the game easy to read and its world convincing.
What to check
Official binaries are paid; source is visible and may be compiled for personal use, but the Aseprite EULA forbids redistribution of compiled copies.