There's not a lot of unknown unknowns in factorio, but one thing which it really captures about software development is your own decisions coming back to bite you, or emergent complexity from notionally simple rules. As your factory grows you'll find yourself wishing you'd built things differently because suddenly something needs to expand beyond what you expected or some part of it is right in the way of a train network. Train networks are really tricky to make work effectively, it's very easy to have deadlocks appearing if you make a mistake, and you might not notice until you suddenly don't have any power because the trail with the coal is stuck waiting at a fouled up junction or something like that. There's a lot of opportunity to debug problems as they appear even in something you designed entirely yourself (and in a multiplayer game it's even more so because you might be detangling someone else's build).

A lot of the process of learning the game is basically learning patterns to reduce this. At the higher level of megabase design it's basically about designing a modular system so you can scale things out as efficiently as possible (and there's lots of possible variations of this).