I really enjoyed the missions and their rewards, and particularly liked the challenge of the Squid ones - even though I'm beyond useless with a Charger in real battles, I managed to get through that series with little trouble (aside from only being able to take out Octolings with my bombs...). Squid's missions, however, genuinely became difficult at times. A few occasions stick out to me.
In one ink-limited mission (the one with invisible platforms), I got splatted completely unnecessarily at the final climb up some tall invisible cubes guarded by a lot of two-tentacles Octarians. Didn't think it'd be too bad an issue... except that was the first time I'd been splatted in this type of mission and I didn't realise that ink lost would carry on across lives. I then proceeded to make one of the most awesome manoeuvres I've ever achieved in this game to redo the climb, being completely evasive around the Octarians (couldn't afford to take them out) and reach the end with literally just enough ink left to get the Zapfish (I mean, I think I had, at most, two shots after I burst its bubble).
Also, the timed DJ Octavio battle was brutal, I found. In theory, it's great, as you can just lie still and wait to be fired at, but... if you mess up about four times (out of, what, 20?), you simply cannot win in time any more. That's the only stage in which I've genuinely been defeated across all of single-player mode, and that two or three times (lost to time on a couple of earlier missions as well, but that was because I was goofing around and trying to collect all of the fish egg currencies).