When comparing Spine vs GrafX2, the Slant community recommends GrafX2 for most people. In the question“What are the best 2D animation tools for game development?” GrafX2 is ranked 1st while Spine is ranked 2nd. The most important reason people chose GrafX2 is:
GrafX2 is scriptable using the Lua language, which can be used to automate tasks and add new functionality to it. The script library features advanced color reduction and enhancement tools, [palette analysis](http://eab.abime.net/showthread.php?t=76519), and much more.
Specs
Ranked in these QuestionsQuestion Ranking
Pros

Pro Integration libraries support most engines
Spine provides integrated modules for 14 major engines including GameMaker Studio, Cocos2Dx, LOVE, MonoGame, Unity, XNA, Flash, HTML 5, libgdx, Corona, and more. Generic runtime libraries are also available for C, C++, Objective C, C#, JavaScript, Lua and ActionScript 3. Dozens of third party libraries support additional targets.
Pro Simplified UI allows for an easy learning curve
No-nonsense workflow allows you to create your artwork in programs much better suited for the task like Illustrator and Inkscape for example, while Spine itself focuses only on the important task of skeletal animation.
Pro Allows for easy use of artwork from third party programs
Spine's developers provide scripts which makes exporting artwork from third party programs much easier to do.

Pro Community-driven feature roadmap
Esoteric Software maintains public Waffle issue trackers to help plan and prioritize feature additions.
Pro Price high for this product

Pro Funded via Kickstarter
Spine received resounding support from Kickstarter backers, beating its pledge goal by over 5 times. A second successful Kickstarter added meshes and other important features.
Pro Scriptable using Lua
GrafX2 is scriptable using the Lua language, which can be used to automate tasks and add new functionality to it. The script library features advanced color reduction and enhancement tools, palette analysis, and much more.
Pro Supports many file formats
GrafX2 supports many file formats, including the popular gif and png, but also importing and exporting from deluxe paint, degas elite, and various other editors using custom formats.
Pro Very large number of tools and effects
Pro Free, open source, and cross-platform
GrafX2 is totally free to use, copy, and modify. It's available on Windows, Linux, Mac OS X, Haiku, AROS, MorphOS, SkyOS, Syllable, Mint, and a few more systems. Basically anything is supported by the SDL library.
Pro Palette color cycling
GraphX2 being based on older 256 bitmap software has inherited some tricks that modern pixel editors do not have . One of them being the ability to cycle color palette and produce animations and effects with it.
Pro Has a great palette tool
You can create gradients from one color to another, work in either RGB or HSL color space, save and load palettes, sort and organize palettes, and even work on "color cycling" images.
Pro Supports tileset addition and extraction
Pro Supports animations
The program has a basic support for animation using frames in newer versions. Graphics can be cloned and copied between frames and changed slightly.
See here how to animate with GrapfX2 https://www.youtube.com/watch?v=Gnq6zBZOqoM
Pro Has a customizable UI with themes support
Theme UI style can easily be changed from settings including buttons and colors.
Pro Drawing constraint mode for vintage 8bits machine
The program is able to enforce the pixel constraints of old machines (C64, ZX Spectrum, Apple II, Game Boy Color, etc.)
For example, in ZX Spectrum mode, only 2 different colors can be used in a 8x8 pixel block.
Cons
Con Spine Professional is expensive
Spine Essential includes nearly all features, except IK, weights, and meshes. Spine Professional is expensive, though it does give all future updates for life (Spine is updated very often).
Con Doesn't support gamemaker 2.3
Con No integration for lesser known engines
Spine does not directly support some game engines, such as Construct 2 or Clickteam Fusion.
Con Dated look and feel
It looks like it was never supposed to be used in the modern world.
Con Lack of modern features
Some modern features that are necessary to do pixel art creation for game dev work are lacking.
