The key obstacle to my enjoyment is the lacking of solid reasoning behind its world-building.
The first impression is not too great. Art is delicious like the cover suggested, but the enticement quickly wears off. Volume 1, like someone else said, is all over the place and not really a great starting point. It goes from rumours of a mysterious game causing deaths in the beginning's setting of a regular city to the depiction of an angsty and violent teenager in love with his blood-related sister (......) and suddenly a bunch of characters show up and it ends on a sort of hanging note with nothing to hook the reader for the next volume (that is, unless you like violent, incest romance thwarted by the archetypal controlling "you're-a-very-bad-child" matron, which I'm surprised to say, is one of the few cases I actually root for).
The story tries to piece itself together later, and does look somewhat interesting with all the peppering of Christian allegories, strokes of inverted morality, mythological symbols and settings etc. But, choosing to focus on "hawt" forbidden romance is perhaps not the best way to bring out character / plot complexity. It is unknown why Setsuna is in love with his sister besides a shaky reasoning given by the story background that he is the reincarnation of angel Alexial, who 1) also had some kind of hots for xir sibling Rosiel and 2) doomed to endless reincarnations of misery. As a reader I can infer that if Setsuna's mother treated him horribly he may have leaned on his sister for support which spurred into love, but I don't believe their backgrounds were given much explanations for grounds of their romance. Sara herself is given even less reasoning for her feelings, being a very naive, pretty, innocent young woman, and basically not much personality, and I personally feel like she is rather akin to...well, you know what I mean. However Sara is a relatively normal and more relatable character than her male counterpart Setsuna, who keeps angst-ing about how miserable his life is despite that the reader feels his angst is rather disproportionate to his situation, as we see his supposedly abusive mother presented as mostly a douche for disliking his violent tendencies and not allowing incest (wow, shocking). I'll give it that she is kind of a dick for not giving Setsuna affection because he appears to be immune to physical damage. Overall their romance looks a lot like teenage rebellion / angst / lust rolled into one, which do not really gain much of the reader's sympathy.
Other characters are even less compelling if their sordid presence provides more amusement than the predictably triggered main character -- angels / God are mostly evil with a few exceptions (Jibriel, I suppose) and demons are usually the "jerk with a heart of gold" archetype. Perhaps the only slightly interesting character would be Lucifer, but unfortunately the manga does not shine the spotlight on him too much. The main villain, God, is a calculating machine bent on destroying the world. Yes, the archetypal villain suffering from a fair share of Disney syndrome. Well, the villain did get an upgrade from your evil mother trying to stop you from romancing your blood-sibling, I'll give it that. The characters also do not receive much development. I doubt Setsuna or Sara has changed much since the beginning (although they might be a bit more mature) and rest of the characters remain unvarying. Characters are essentially reduced to reincarnations of very monochromatic set of emotions -- Setsuna, angsty and violent-prone. Sara, innocent. Katan, loyal to a fault. Mother, cold and unloving. Alexiel, you're basically a plot-device...you get the idea, characters can be summed up in one or two sentences or even a few words.
The second most focused element of the story is violence, but like my English teacher once said, "do not use swear words, or even words, without good reason". Much of the violence is in essence rather Hollywood-like, thrown in for shock value to lure the crowd than carrying actual emotional weight. I'm not saying all of the violence is such, but too much empty violence can desensitize the reader when they are actually supposed to care.
Lastly the manga does not offer a particularly self-contained world view. For example, what is the relationship of this God with the deity in our world? If heaven is full of evil beings and hell reversely, what impact does that have on the humans? Do they believe in a parallel angel/demon view of ours, or an inverted one? How did a computer come to rule over magical creatures? Why was Sara taken to heaven instead of hell? What is the purpose of the subplot of Sandalphone gaining a body through Sara besides trying to add an obstacle to the sibling-romance reunion?
The story suffered due to the lack of reasonable characterization (I say reasonable as in within the bounds of most reader's expectations, as there are those who have different expectations of reason). It also suffers from excessive brashness and lack of coherent world-building. It could be seen as beautiful and complex at a glance but in reality leaves very little afterthought. Unless your stance is that most manga don't leave behind much afterthought (which I do not believe), this makes Angel's Sanctuary subpar of real masterpieces and falls beneath an average work of art in the process of doing so.
Of course, the above is purely my opinion. I can see why some would enjoy it -- just wasn't much of a thrill for me, for the above reasons.
