Unity's a bit slower than other engines. But not graphics-wise, as far as I know. It's the garbage collection, scene graph/reference lookup/GameObject system and other weird quirks with Unity's version of Mono you need to keep an eye on, as far as Unity's performance differences go.
I'm not sure if you're aware, but Unity is a 3D engine. It renders 2D stuff as flat quads in the 3D world. This is nothing unique to it.
Even other fast 2D engines use 3D (OpenGL or DirectX) to render.
Spine-Unity (and other performant Spine runtimes) use meshes to draw skeletons, even if you don't define them as meshes.
Spine generates polygons and vertices and have polygon counts just like 3D games do.
So my point was: whatever performance limitations 3D games have to abide to, you also have to watch out for when using Spine in Unity, or any skeletal animation system in any modern engine for that matter. That's why checking out 3D games on your target device is can be your starting estimation.
The hand-wavy difference is that 2D involves alpha-blended textures which can be slower than just straight up opaque textures on 3D. How much of a difference is really up to you to test and work with: how complicated you want your shading to be compared to the 2D or 3D games you see, if you want lighting or some other fancy things or not.
