This is based on opinion. Please don't list it on a work's trope example list.
Tear Jerker / Star Ocean: The Second Story
One of Rena's death cries is a delirious, soft "...Mother?"
One of the first towns you get to is promptly destroyed by a tidal wave. Before this happened, you introduce a Lonely Rich Kid to some neighborhood kids and teach him to be friends with them. Not long after he makes friends with them, the town is destroyed by a tsunami. While he survives, you notice that one of the kids is missing along with most of the town in general, who had almost no warning that there was a tidal wave coming their way. If they weren't crushed by wreckage they were swept out to sea with pretty much no hope of rescue.
Opera and Ernest's situation - like Claude, they're not from Expel and are stuck on an underdeveloped planet. If it weren't for Claude, they would have no hope of getting out short of stumbling across Precis. If you recruit only Opera, then she has to live with the knowledge that Ernest is dead, and she doesn't know that he can be revived. If you miss out on both of them, then they die when Expel blows up.
Leon's parents are implied dead because they Never Found the Body. If Claude tells him to wait at the village? Then Leon dies too. If Rena is your main character? Then Leon possibly is lost because they Never Found the Body. (Granted, canonically he survives, but so do all the playable characters.) Fortunately, they show up in Leon's solo ending.
Is your main character Claude? Then Dias dies.
Consider this for all your Expellian characters: When they get the news that Expel is gone and that there may possibly be no way to ever get back, think of what it means for them: Celine, Precis, and Bowman's families are dead. And Bowman was married, while Precis is 16. Leon meanwhile is only twelve when he goes through this. Dias may be able to endure because he is The Stoic and he already lost his entire family anyway, but consider that he also has nightmares...
Oh, and given the number of native Expellians you recruit? As little as one Expellian could have survived. While Expel gets better, this leads to the next bit...
At the end of the game, Nede performs a Heroic Sacrifice. There is no way to evacuate the citizens. Only the eight who fight the ten wise men survive... among them can be as little as two Nedians, Rena and whoever you recruited. They say in the ending that "You will be the last of the Nedians", and Chisato and/or Noel look sad and say "Yes." Did you get Welch, by the way? Then there will only be two potential survivors. So there is once again an Inferred Holocaust... and there are potentially millions of Nedians who will give up their lives... It's fully possible they knew this... but what if they didn't? That doesn't make it any less disturbing.
Oh, you know Chisato and Noel? What happens if you have seven characters by the time you get to Nede? (eg, did you recruit Welch?) Then There will only be two Nedians who survived the destruction of the homeworld... if that second one is Chisato, then the Nedian race will go extinct. There was one man who you could have saved too... and the last thing you told him to do was "Take care of the animals." Even if Noel survives... the only way for the race to make it to another generation is for him and Rena or Chisato to hook up. Which might actually not happen since Rena can easily hook up with Claude, and canonically does according to the obscure sequel. And if you know genetics? All this does is delay the inevitable unless there is a way to reintroduce genetic diversity. Indeed, four-hundred years later it's all but spelled out that Noel and Chisato's descendants have been absorbed into the Expellian race. The player even meets one who is very obviously directly descended from Noel.
Aww how cute, you saved the last wild Psynard... and it was even a mommy, too. So cute. ...too bad it won't survive the game. Meaning that alongside all the other wildlife of Nede? It's extinct.
Literally every single living thing you meet dies, save for those you recruit. And roughly half of the people you meet will be Killed Off for Real.
Then, of course, there's the whole story behind the Ten Wise Men and their reason for being in this state in the first place, providing with some Sympathy for the Devil (maybe except Cyril). They were created to surpress rebel forces that were rising up against the Nedians when they ruled the universe as a military dictatorship. Then when their creator's daughter died, the military tried to hide that information. Lantis eventually found out and was Driven to Madness, reprogramming the Wise Men to annihilate the universe. When that failed, Lantis was Driven to Suicide after sealing his cyborg weapons for 4 billion years and transferring his personality and that of his daughter to Indalecio and a Filia clone. And their damage did so much to the Nedians that they were forced to take refuge in an energy mass and completely erase the history of the whole disaster.
The death of Ronyx, one of the more amiable characters in the first game. Just to be a dick, Indalecio/Gabriel decided to test-fire the Wise Men's main cannon to Calnus all while the party watched. Slowly, little by little, Calnus' shield starts to dissipate, and from each fire, Indalecio/Gabriel orders the cannon power to be increased. Claude couldn't do anything as Calnus was on the last lines of defense, and he ended up begging the Wise Men to stop. Again, Indalecio/Gabriel didn't even flinch and orders yet another empowered shot, which wiped out Calnus AND Ronyx inside... all while Claude watched. As far as Claude's concerned, This Is Unforgivable!... unfortunately just when he and the party are about to deliver vengeance, they got wiped out by Marsilio/Zaphkiel because they don't have the correct weapon material.