You can also do the 2.5D style of like Trine or Mandragora.

A lot of 2d games are done in 3d engines these days anyway, because it gives “free” parallax, depth buffering and masking, hardware accelerated compositing etc.

So it’s all the work of hand-drawing animation frames with all the complexity of rigging and mapping in 3d.

Enter the Gungeon and the Shovel Knight series are two examples that come to mind.