When comparing Unity 2D vs Puppet2D, the Slant community recommends Unity 2D for most people. In the question“What are the best 2D animation tools for Unity?” Unity 2D is ranked 1st while Puppet2D is ranked 7th. The most important reason people chose Unity 2D is:
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.
Specs
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Pros
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.
Pro Mesh Deformation
Instead of having to change sprites to bend legs or other joints mesh deformation changes the mesh shape based on joint weights to bend and move.

Pro Inverse Kinematic bones
Bones will move and rotate reacting to the position of the rest of the skeleton. The animator does not have to animate each part of a joint but rather have it follow realistically. Also can be used for ragdoll effects based on physics.
Pro Built on top of Unity’s animation system
Mecanim and state machines work natively since Puppet2D builds on top of Unity’s built in animation system.
Cons
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.

Con Forced editor scaling causes problems
Puppet2D adjust the scaling of bones in the editor for display purposes, which results in unintended behavior if other objects use a bone as a parent.
