Spac(emacs) with pdf-tools has convenient default keyboard shortcuts (e.g. vim-style with spacemacs) and has potentially the best annotation support, as combined with the org-noter (or interleave) package annotations are automatically exported to a notes file and backlinked. Through spacemacs, pdf-tools is easily installed and configured. Because it is an emacs package, the reader is ultimately configurable and hackable.
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Pros
Pro Extensible, customizable and scriptable
Being a Emacs plugin you can use elisp to customize, script and extend pdf-tools.
Pro Can treat multiple PDF's as one big PDF
Pro Nice search using Occur
Occur creates a list all lines matching a regexp or string in one or more pdfs and allows easy jumping between them. Really helpful when searching long documents like datasheets.
Pro Synctex support
Pro Easy installation
Although installing requires little more work than stand-alone readers, pdf-tools is very easily installed via Emacs 'list-packages' or even easier as a layer in Spacemacs
Pro Convenient default keyboard shortcuts
Uses emacs or vim-style navigation (via spacemacs/evil. Shortcut overview via transient state "SPC m .")
Pro Automatically exported notes
Notes can be exported automatically to and backlinked from an external org notes file using the org-noter or interleave package.
Cons
Con Only for power users
Handy only for people that want good notes/annotation management. Otherwise using any other pdf-reader is recommended.
Con Too cumbersome for quick reading or annotating
Although setting up pdf-tools is not too much work. For quick reading using some default pdf-viewer like evince/okular/zathura is recommended. Also, except for the auto-export feature (with org-noter/interleave package), other editors like e.g. pdf-XChange Editor (via wine), Okular or mupdf have even more powerful annotation features.