The destruction of Lalna's castle at the end of the apprentice and the start of Galacticraft is downplayed, but still hits quite hard for those who've seen Duncan's tekkit series. The castle was second only to Sjin's farm in scale, and had even more valuable resources and advanced machines inside it, after all the work Duncan put in, and then it is completely ruined in an instant
Later on, Duncan finds the tainted ruin of the castle, and considers reclaiming it for a while, before deciding that it's time to move on. He and Kim then give the castle a proper send off, blowing it up with waves of missiles from Panda labs. YMMV on whether this is a consolation for the original loss, or another tear jerker in it's own right.
In episode 17 of Flux Buddies Kim and Duncan continue their raid on the Dwarven base, which they deemed evil due to all the stereotypical tells (rooms made of Netherack, lava, darkness, etc). Except when they open the chests, expecting to find great loot just like in the previous dungeon... all they find are food supplies. Meanwhile the dwarves are chatting and hanging around and only attack when provoked. The two of them spend the rest of the raid guilt tripping.
In Episode 25 of Flux Buddies, Duncan and Kim are trying to move their cat, Tiddles II, into a new home, and they do so by using Nether Portals. They land in a house, and Duncan can only watch as Tiddles II walks off the platform and falls into the lava, dying instantly. The fact that Kim chews Duncan out for it only makes it worse.
While the war against HAT films at the conclusion of Flux Buddies is a crowning moment of awesome more than anything, and Kim and Duncan consider it a victory, Panda Labs is completely demolished, first by railgun fire and then by rejuvenation missiles. Seeing Kim and Duncan's home destroyed yet again is a sad moment, and drives home that this is the end. Particularly sad considering how homey they tried to make that base, compared to their previous one.
Flux Buddies 2.0
Crossing over with Nightmare Fuel at the same time, Episode 55 of Flux Buddies 2.0 features all of their beloved Chocobos being brutally murdered by Lalnable Hector.
Episode 80 has the secret Cloning Lab, again crossing over with Nightmare fuel, given that it has several flawed copies of Kim contained in it. the Tearjerker, though, is how upset and unsettled Kim is by the entire thing, and not even using the SPAMR launcher to destroy the room seems to help.
Flux Buddies 4
Episode 29, The Sacrifice. In the previous episode, Mother had tanked a plutonium nuke, the most powerful bomb that can be built in that modpack, like it was nothing. Duncan resolves to build a second, less-powerful nuke from uranium, in the hopes that the first bomb injured mother somehow. Kim, knowing that Mother was a part of her and vice-versa, comes to the conclusion that the only way to kill Mother is for her to die as well, and thus gives a short speech to Duncan as they set the bomb telling him about what he means to her, and to take care of himself, and finally giving him a sapphire to remember her by, and sending him away with a portal gun while staying behind as the nuke ticks down. Fortunately, it works.