Coming together for the first time since Yaegerists took over Paradis Island, Eren cruelly accuses Mikasa of being biologically attached to him. The Ackerman clan were genetically engineered to protect, and when that latent power awakens, they have no choice but to obey (according to Eren).
At the time, her serenity seemed odd. But according to Eren, this act ultimately freed Ymir. It was Mikasa all along who was meant to do this, not him. Therefore, everything he did was to ensure that she made the choice to kill him, ending Ymir’s existence in the process, thus, eradicating Titans.
Being one of the first times Eren used his Titan powers in the field, he lost control, punching at Mikasa shortly after transforming. The fact that he almost killed one of his closest friends, as well as one of humanity’s finest soldiers, is what makes this moment so horrendous.