Alright, since I’m still stuck on my sci-fi story because I can’t exactly outline the mid-point plot twist with a realistic catastrophe on board an interstellar spaceship, I thought I’d widen the scope a little — towards full-on open brainstorming:
What, if anything, can realistically go wrong on an interstellar journey? 
(By “realistically”, I mean “without making any extra assumptions about aliens, unknown forces of physics etc.” — just based on what we currently know.)
I may have underestimated this challenge a little because, in real life, at least based on our current knowledge, there are of course several huge obstacles to interstellar travel: fuel and food supply, achieving a travel speed that makes the trip feasible (i.e., a significant portion of the speed of light), radiation, dust particles and micro-meteors, etc.
The problem is that all of these challenges are so big that, if a ship cannot handle them, there’s no point in it even leaving the solar system. For example, a micro-meteor hitting the ship out of nowhere mid-journey should not happen, because the ship will need some kind of deflector system anyway to deal with stuff like this countless times per day. And if it has a deflector system, but it randomly fails when the story needs it to, the resulting collision, given the intensity of the impact, for all I know wouldn’t just severely damage the ship, but would probably destroy it completely.
So these disasters are all kind of “too big”. When you have a story set on Earth, and you want to create a challenge for your characters, or come up with some catastrophe that leads to some severe casualties, you wouldn’t immediately jump to “meteor hits Earth and wipes out all mammalian life”, would you?
Once all of these major challenges are out of the way, though — those that wouldn’t even make the journey worth starting if they hadn’t been dealt with in advance — the emptiness of the interstellar medium, as well as the inability to stop without wasting fuel or exposing the crew to unsurvivable g forces, create a pretty non-interactive environment for any story set between two stars.
Even internal failures of the ship aren’t that easy to create. A hull breach, as it seems to happen quite frequently in Star Trek (or even more vividly in one episode of The Expanse), shouldn’t happen too easily, either: Not just because even minor collisions with dust speckles have to be avoided anyway; but also because the ship hull will have to be thick enough to shield everyone inside against radiation. And one effective way to do that is to place a layer of water between the hull and the interior.
Now it’s hard for any given crew member to just be “randomly blown out into space”, if there’s a thick wall of water in between. You could of course have that water seep into the ship, but most likely it would not happen in such quantities that anyone would drown in a corridor or something.
Radiation, even if the ship’s protective measures against it may fail to some reasonable degree, would be comparatively slow to kill humans — probably slow enough for the crew to notice the holes in the protective layers in time to patch them up.
Finally, deliberate human sabotage is also hard to justify — since anyone with such intentions is stuck on board the ship together with everyone else for the time of the journey. Even people with malicious intent still have survival instincts.
So, what likely “medium-size disasters” do we have available at all? It seems to me like I only have the choice between “something that would destroy the entire ship” and “nothing at all happens, because the ship can’t interact with anything around it”.
The reason I'm asking is that two characters could have been killed by such a water jet; I watched a video yesterday where somebody demonstrated with a dummy head what would happen if a waterjet cutter came into contact with the human body.
), so you would have to look elsewhere for ideas.
