SpaceChem
I've mentioned how SpaceChem's challenging, engaging mechanics (and great soundtrack) overcome its humble production values, but that isn't the reason I spent so much time in it. SpaceChem's story mode has 49 missions - plus a few optional ones - distributed among three types: Research (single-reactor puzzles about micro-managing chemical compositions), Production (multi-reactor puzzles which add resource management and general complexity), and Defense (boss battles! which toss in some sensitivity to timing and real-time interaction). Maybe 49 doesn't sound like a big number, but when you consider that many of the later missions have several parts and can take a few hours each, there's a lot to do. Both the variety of content, and the sheer amount of it, is intensely impressive.
And then there's also ResearchNet, which is regularly updated with new designer- and user-generated puzzles. These even use some base mechanics that aren't included in the campaign missions, like Fission.
This is a greatly entertaining and challenging puzzle game, and the content-to-dollars ratio is simply amazing. Get it!
Better than: Planet Puzzle League
Not as good as: Portal 2, if only because of JK Simmons
Optimizing solutions is also pretty satisfying: especially when I can make my friends' scores look bad.
Progress: Finished all the campaign levels