This is based on opinion. Please don't list it on a work's trope example list.
Tearjerker / Karakuri Circus
Masaru has been through more in just a few months than most adults go through in a lifetime.
Pretty much all of the hospital arc. Made worse by the cheery beginning.
Mark's collected drawings...including the single, lonely wing.
The end of the Sahara battle. All the participating Shirogane dies, Narumi lost all his limbs, which were replaced with puppet limbs, and it's all for nothing, given the Francine they fought wasn't even the real one.
Francine - Both the human woman and the doll made to resemble her. So much pain, anguish and tragedy happen in both their names and both of them suffer that weight horribly, only finding some kind of relief in death.