Popotan/Tear Jerker

• Mai having to leave Konami in episode 2. The image of her running away, doing her damndest to fight back her tears, really sets the tone for the rest of the series.
• At the end of episode 5, the mansion jumps forward in time without Mai and Mea, forcing them to wait five years for the house to return. In the next episode, it's revealed how Mai has spent this time: she's graduated high school, become friends with her classmates and has finally been able to live normally without worrying about losing her new life. The problem? She hasn't aged, neither physically nor mentally, and has to wear a wig to keep up the charade. She gets found out when Mii accidentally knocks it off. When she finally understands that she will never be able to have a normal life as long as her journey is unfinished, she and her sisters do the same thing as the audience: cry uncontrollably.
• Nono's grandfather all but disowning her for decorating the shrine with Christmas ornaments.
• The end of episode 9. Seriously. It's bad enough that Konami has died young waiting in vain for Mai to return, sending the latter right back into her depression, but she also happens to be voiced by in the Japanese version by Tomoko Kawakami, another person who died far earlier than fair.
  • Mai's reaction to this is shown very clearly in the following episode, and it's just as heartbreaking.
• In the penultimate episode, the girls learn that they can end their journey, at the cost of living far away from each other. Despite Mii's best efforts, Mai seizes the opportunity and goes back to Konami's time period, leaving behind nothing but a note of what she's done. Mii soon follows suit, and Ai and Unagi, having no reason to travel anymore (Mea presumably being frozen in time elsewhere by Keith), end up going away as well. The music doesn't help.
  • Making matters worse: wanna guess who is the first person to find Mai's letter? That's right, it's Mii.
• And finally, there is the very last episode. The sisters are living their own lives together with the people from earlier in the series they cared about the most. However, they realize that they can never truly be happy without each other, and to say that they are unhappy with the current situation would be an enormous understatement. Thankfully, it at least ends on a happy note.