IIRC Mayuko never once talked to Yorito nor Aono. The only person she is close to other than Takeshi is Matsuri. So I believe out Of the 3 people involved, only Matsuri's sacrifice will make her concern enough to want to step in and stop her. That's why she left, because she knows Matsuri is dead serious and she can't persuade her otherwise. Secondly, she can't bear to watch it any further. However the interesting thing I've just realised is that Mayuko's feelings could set herself up for a surprising return. What are the chances of her reappearing just in time to put a stop to Matsuri's crazy plan? I think it's 50-50.
I've also thought over the reason why Yorito would agree to Matsuri's sacrifice.
Ok, now here's a piece of speculation I thought of. Just be warned that after I read through it a few times, I think it isn't good. The ending is unsatisfying and anti-climatic. I guess there's really no way that a happy ending can fit is there? Moreover, it does not link back to Yorito's promise to show Matsuri the blue sky. And oh some of my ideas are similar to what johnishida posted.
Spoiler for speculation:
What if the result of the plan is not what Aono wanted? Considering how Aono has always wanted to be with Yorito, would she be happy if Yorito doesn't exist in the future/past that is planned for her? Wouldn't she try to break herself from this future/past or perhaps Mayuko will come just in time to save both Yorito and Matsuri from the need to sacrifice? Maybe the three of them can really live together after this. Aono realise that Matsuri had always been very remorseful and she forgives her. The 3 of them lives happily ever after...
*duck rotten eggs*