When comparing Piskel vs Blender, the Slant community recommends Blender for most people. In the question“What are the best 2D animation tools for game development?” Blender is ranked 5th while Piskel is ranked 15th. The most important reason people chose Blender is:
Blender is licensed under the GPL. Some Blender modules such as the Cycles rendering engine are licensed under the Apache 2.0 license.
Specs
Ranked in these QuestionsQuestion Ranking
Pros
Pro Works in any browser
WPiskel is HTML5-based so it works in any modern browser.

Pro Animation support
Piskel includes onion skinning, exporting to sprite sheets or gifs, defining frame rate, and present live playback.
Pro Sleek interface
It is also easy on the eyes.
Pro Very simple for beginners
Once you get the hang of it its a very powerful tool
Pro Offline versions available
The downloadable version of Piskel (built with node-webkit) is available for Windows, Linux, and Mac OS X.
Pro Easy to use lighten and darken tool
With the click of a button you can create amazing shading.
Pro Enough tools to be powerful
It has enough tools to be powerful, but not too many to put off beginners.
Pro Open source
Piskel is licensed under Apache License, meaning that the user can use the software for any purpose.
Pro Has a straight foreward tile view mode
... so you can instantly see the result while drawing tiles


Pro Free and open source
Blender is licensed under the GPL. Some Blender modules such as the Cycles rendering engine are licensed under the Apache 2.0 license.

Pro Wide import and export format support
Support lots of modern 3D formats including DAE and FBX - ideal for game developers.
Pro Has a powerful rendering engine
Blender runs the Cycles path tracing engine under the hood. Cycles is a very powerful rendering engine capable of full path tracing (light fall off, caustics, volumetrics). It is mostly compatible with OpenCL and CUDA rendering, and is implementing mycropolygon displacement features. The upcoming release has a viewport engine called EEVEE whereby you can see and interact with your work in render mode in real time!

Pro Python extensibility
Blender embeds Python 3, which can be used to write add-ons, tools, extend the interface, rig characters and automate tasks.

Pro Powerful animation suite
Blender provides a full rigging system, and automates animation by interpolating between keyframe positions.
Pro Supports both low-poly and hi-poly modeling

Pro Regular release schedule
Releases are made every ~3 months.
Pro Sculpting and 3D painting features
Although Blender's 3d painting and sculpting tools (mostly painting) are not at par with specialized software like Substance Painter, ZBrush, or Mari, it is more than capable of getting most jobs done if the user takes the time to learn and understand it.

Pro Includes video editing & compositing tools
Blender's node-based compositor has comprehensive video sequencing and post-processing features.
Pro Node based modeling support
Pro Keyboard shortcuts
Good keyboard shortcuts for everything. Keep your left hand on the keyboard and your right hand on the mouse.
Pro Very useful for a freelancer
It offers a round solution (it covers many areas and professional fields) for a freelancer, for free, constantly updated, very polished, and allowing high quality results that clients do require. After some learning, it becomes very useful for professional work.
Pro Has a large community
There's a huge community to help you get started immediately.
Pro Coherent and streamlined workflow / internal use logic
The trick with Blender is to get used to its usage philosophy, as it keeps consistent through all the application. Once you get it, every feature or addition is learnt naturally, almost effortlessly.
Pro Very versatile
You don't have to switch between software when you want to do different things. Because modeling, sculpting, composting, video editing etc can all be done in blender.
Pro Generative geometry using nodes
Cons
Con Lacks a true resizing tool
There doesn't seem to be any decent tool in Piskel for an easy stretch or shrink. The only ways possible is resizing the whole image or importing and image and shrinking it from the export tool.
Con No button for undo
Have to use ctrl+Z.
Con Rotation is limited
Rotation is only made in predefined angles. Does not support variable rotations or mouse based rotation. Does not support rotating selected areas, only frames-layers.
Con Shading by hand
Shading can be difficult.
Con Doesn't work well with drawpads
In the online tool you can't draw lines at all, yet using a graphic tablet, being in the offline version controls are pretty chunky and everytime you start drawing a line, the screen flickers black for a short period of time.
Con Too many possibilities, no unified workflow
The operations are not optimized enough for specific tasks.
Con The physics engine is a bit lagging behind, especially the destruction physics
Con Difficult learning curve
Blender has a history of being unintuitive, but the 2.8 overhaul made the program far easier for beginners to pick up, and changes continue to be made to further improve the experience. However, there is still a learning curve.
Con Not good for Industrial Design because it uses average vertex normals
You can not create a hard surface with a radius continuity degree along a surface using a specific radius value.
Con Vertex normal issues on edges after boolean operations.
After creating a simple boolean operation the vertex normals are broken. A lot of work to fix the issue and you loos surface continuity.
Con Bad vertex normal after boolean operations
Does not handle well polygon intersections. And need tweaking by hand points or adding average vertex normals via modifiers.
Con Does not handle NURBs
Is not capable of real hard surface for industrial design because is not able to reproduce surface continuity degree as a NURBs does and average vertex normal destroy surface radius.
Con Poor particle system
The Blender particle system can at times be a little limiting and finicky (and buggy) to get working. Even if it can get most straight forward jobs done, it is far from the most advanced system, and could benefit largely from advancements.
