I had the same situation with an 2d artist, not pixel-art but just painted stuff in Photoshop. We wanted to do an isometric game and after he started working on some characters , we came to the conclusion that he had to do not 4x times the work, but almost 5-6 times the amount of work for each character (walking cycles from 4 different angles).
The 2nd approach has to make the 3d characters and animations in 3d, paint the UV maps so they look stylished.
I think If I wanna make a pixelart game, I will first model the main characters in 3d, and make the pixelart on top of the rendered animations