Episode 15 is just one giant tear jerker for Mizuno fans everywhere. Especially when Mizuno comes to the realization that Takuto doesn't love her the way she loves him (or even the way he loves Wako) and it depresses her so much that she stays on top of the bus in the rain, when she snaps at Marino and causes her to disappear when their/her mother has returned to the island and is looking to stay with them, and when Mizuno finds herself caught in an Endless Loop when she tries to leave the island, driving her into a Heroic B.S.O.D..
The ending scene of Episode 16, though it turns into a Heartwarming Moment at the very end.
Episodes 14, 15, and 16, in addition to being a Wham Arc, all had their fair share of tear-jerking moments. Most of them did indeed involve either Mizuno or Marino in one form or another.
In Episode 20 we learn the deal Head's apparent right hand man Ryousuke had to go through, and it is sad. And the man still helps Head or probably hopes to bring back the brilliant artist he knew after all that.
Shingo's whole fate, if you think about it. Not only does he appear to have been manipulated very easily by Head, the way we only see Head visiting him in the hospital, as well as the fact that the latter is able to move him to his house seemingly without anyone of Shingo's family stepping in seems to suggest the guy doesn't even have anyone but his beloved Head. It's very possible that Head exploited this very loneliness for his personal gains to make Shingo give him his mark. Then there's the fact that the guy has been in a coma for fifteen whole years. While we don't really know what caused it, for a person to be unconscious for so long, it has to have been something rather severe. And once he wakes up, Shingo talks about his troubles with becoming an adult, which apparently promted him to apprivoise and activate his First Phase. However, that seems to have backfired as he's been "left behind", as he puts it. In the end, he seems to have regretted his decision to stop his aging process and unwittingly provides Head with the means to kill all life on Earth. Which also includes Shingo, as without the protection of a mark, he would have died together with the rest of mankind, and there is nothing that hints Head would include him in his "glorious past" he wants to relieve. The poor guy had his troubles and feelings manipulated and exploited by Head to the point of falling comatoes and his "reward" for fighting his way back into life was (almost) death at the hands of the man he loved.