When comparing Spine vs Unity 2D, the Slant community recommends Spine for most people. In the question“What are the best 2D skeletal animation tools?” Spine is ranked 1st while Unity 2D is ranked 5th. The most important reason people chose Spine is:
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.
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 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 Price high for this product
Pro Built into Unity 4.3+
2D game creation was a major feature request from the Unity community and was added with version 4.3. 2D is provided in both the Pro and Free distribution of Unity.
Pro Integrates with Mecanim
Mecanim brings state machines and blending to 2D bone animation. The state machine editor allows for designers and programmers to visually create a Finite State Machine (FSM) to control when animations should play. Mecanim also allows for blending so an animation can transition smoothly between two states without the need of in between frames made by an animator.
Pro Sprite Sheet and Bone based animation supported
Both types of 2D animation for game development are supported in Unity’s system and can be used interchangeably in the timeline.
Pro Easily change sprites dynamically
Usually used for character customization, programmers can change any sprite in a bone animation at runtime easily by referencing the bone and loading the new sprite from the resources folder.
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 Requires EVERY developer to have a license
Ever developer needs a license, not just the animator, or an overall license for the project. The license agreement is extremely restrictive.
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 Lacks critical features
- Vertices can't be animated, so you can't have ANY organic feel (like... lungs breathing).
- Parent bone can't be animated without affecting the children. This is especially impeding for organic feel, again.
- No option to show & unshow assets (or it is hidden), like for switching weapon on your character for exemple.

Con Poor script interface for texture atlases
Accessing individual sprites within an atlas texture is possible at runtime, but requires use of the Resources folder subsystem.
