I had problems trying to apply a wave-like localized effect on a loop atop another moving path.
E.g. a waving snake which follows a path to do u-turns and so-on.
The first being that keeping the waving motion looping was very hard - I had to procedurally generate points for my wave spline, then hand-add them to the .json file. Secondly, making all of the motion local space motion, while still having the underlying body follow a spline didn't blend well - when animations transitioned from one to the other, I couldn't transition from one path to another without snapping, which required full blending off the current path, then blending on to the next.
Finally, a lot of my game was involving the snake folllowing an electrical cable or wire - and I couldn't figure out a nice way to provide that cable or wire to the Spine object via Unity.
No doubt these are probably solvable, but it was challenging and I had to give up on it for now. I even hired a college student to focus on the problem and he melted and disappeared.