Have you tried Infinifactory (3d FPS ala Portal + assembly lines)? I loved Big Pharma and its not exactly the same, but it felt like the same parts of my brain were working on it.
I think Infinifactory is mind-blowingly amazing on many levels - an epic triumph of game design. The components are few and simple, but provide enormous combinatorial possibilities. There's a logic-language and aesthetic that emerges, that includes the very things patio11 mentions: input ratios, timing, and pipeline issues. The puzzles are sequenced so that each level is initially shocking, but gradually yields to the player's contemplation and experimentation. I think I've had more pure delight from this game than from any other.
I liked TIS-100 a lot too, and Infinifactory is kind of like a visuospacial, high-production version of it.
I remember playing 'KOHCTPYKTOP - Engineer of the People' years ago, and loving it. I've also really enjoyed SpaceChem, Infinifactory, and TIS-100. All around very interesting and challenging games.
Currently working my way through this and it's awesome. The simplified 'transistors'are more like relays but since I want to build a relay computer some day, that's perfect. :D
You would enjoy pretty much all of the games by Zachtronics, including Infinifactory. They're all puzzle-oriented though, as far as I know, rather than sandbox.