Blame!
Blame! (Pronounced as BLAM) is the work that put Tsutomu Nihei on the map. Originally releasing between 1998 and 2003, the series did not reach critical acclaim, but it did create a Bladerunner-esque cult following which was -arguably- critical for his later success with "Noise" and "Biomega". The hallmark of these series is plentiful use of black ink, with strange and abstract architecture on a gigantic scale. Blame follows the journey of the protagonist "Killy", a posthuman living inside the "The City", a Dyson sphere-like construct which has grown so large that it has enveloped the entire solar system.
What follows technically counts as spoilers, given that it is drip fed throughout the story and only becomes fully apparent by the manga’s conclusion, so if you want to go in to Blame! mostly blind then you should stop reading here until you have finished the series.
Killy's goal is to find a human who possesses the "net terminal genes" (NTG), a set of genes that enables the automated control system that runs the city to recognize them as a human being and legal resident of the city. However, this is no mean feat, as over many (Hundreds? Thousands? Tens of thousands?) years, mutation has eliminated the net terminal gene from most of the remaining human and post human population. This is what has allowed the city to grow out of control and is also the reason that human beings without the NTG must live away from the sight of the automatons which run the city.
Finding a human with the NTG is believed to be essential for restoring control of the city to humans but there are other denizens of the City who actively try to prevent this, as they have diverged sufficiently from baseline humans as to be another species entirely. These are the "Silicon life", a group of cyborgs distinct from humans and also not affiliated with the safeguard- a type of robot police the City uses to remove intruders. Throughout the course of the story Killy meets several characters, usually humans living in squalor throughout the city. Though Killy is the protagonist, Cibo is perhaps more important for the reader's understanding of the story as she has by far more meaningful dialogue.
I have been deliberately vague about characterisation and that is because almost everyone that we see in Blame is some kind of post human with motivations that are unclear. This serves to add mystique to the story, but I imagine it left many readers feeling detached from the characters and even the story as there is no real emotional core. Though some people will not enjoy Blame! as a result, this detachment really works with the artwork to depict a bleak and barren world in which humans are not the main focus.
Blame! looks very different from more modern Tsutomu Nihei works like Knights of Sidonia, Aposimz and Kaina of the Great Snow Sea, so I would recommend starting here if you intend to read more of his works. The reason for this is that whilst the art has a rough appeal to it, if you are used to more refined art then you may find this a downgrade. Nihei himself claims that his more recent works that focus more on character interactions and relations would not have been possible with the level of artistic skill he had during the writing of Blame!, something that diehard fans might find controversial.
As for me, I find Blame! to be a masterpiece of setting and worldbuilding and though it may have moments where the story is unclear or the characters look misshapen, overall I enjoyed it enough to shell out for the master's editions and would encourage you to check it out.