The first time I saw a picture from Angel Sanctuary, it was the one to the left. Well, this was the first one that caught my eye. I thought Setsuna was a girl, partly because of his name (Sailorpluto's name was also Setsuna and I was into Sailormoon a lot at the time) and partly because of his apparence in several other pictures. I figured it was a shoujo-ai story, which didn't really bother me. After investigating it more, I found out he was in fact a boy. And then the story disturbed me.
Setsuna Mudou is Sara's brother. He's in love with his sister and she returns his feelings. This torments both of them, whose mother is obviously a devout Catholic. She divorced their father and in the first issues of the manga, plans to move with Sara to London to keep her away from Setsuna, whom she regards as evil. Sara knows that when she goes there, she will finish school and then marry a son of her mother's friend, which she doesn't want to do.
Sara can't hide her feelings and neither can Setsuna. His destiny is no match for his determined love. He wants to protect her and keep her out of danger, but is unsucessful. For a while, he explains that he was only kidding when he told her he loved her and that he couldn't feel that way about her. Sara didn't believe him. He had kissed her when he thought she was asleep and she can't stop thinking about that. Setsuna stops her before she leaves for London (just barely) thanks to Kira, and the two run off together. That, however, is only the beginning of their tragic story.
When I first read it and realized that they were siblings, I was a little weirded out to say the least. But there are various reasons it stopped bothering me almost right away:
1. They're fictional. Fictional characters can get away with doing more than real people. That's what makes fiction so much fun. (Lestat, for example, loves his mom in a not-so-motherly fashion.)
2. The reincarnation thing can be used as an excuse. Because of Setsuna's past life as the Organic Angel (and the fact that Sara is really the current reincarnation of the angel Jibrille), perhaps their current blood ties don't mean as much as they should.
3. Their love is obviously very true and very deep. I may not be able to love my siblings as more than brothers, but true love knows no boundaries. Be it gender, be it distance, be it bloodline. Sara dies for Setsuna and then he in turn goes to Hades to retrieve her soul (it's not there, but his willingness to go that far shows how much he loves her).