Some things off the top of my head that I find annoying:

- Puzzles start feeling like they're asking more for busywork than for puzzle-solving. I enjoy thinking about "how do I do this?" I don't enjoy thinking "well, I know exactly what I want to do, but it's a huge slog to actually go through the motions."

- You can't rotate the thing that accepts a polymer. So if you end up making the correct thing, but your orientation is off, you get to manually re-lay every part of your machine, instead.

- Everything uses the same clock.

- You can't even apply purely mechanical fixes for everything using the same clock, like a three-arm grabber with one of the arms cut off. There goes the conceit that the rules are justified by the theme.

I like that Opus Magnum scores you separately on time, space, and monetary cost. That was a good idea. I like working out fundamental minimums for how quickly I can produce something (based on the source pieces I'm allowed...) and designing something that can achieve that. The animation of a completed machine is fun to watch.

I think the monetary-cost mechanic seems underdeveloped.