Hm, I'm going to guess that the Kindle is probably the most popular e-reader, and it has the ability to add notes, highlights and bookmarks, both with the hardware device and in the apps for tablets and computers. It also doesn't have the eye strain issue.

Actual remaining issues:

* complex layouts get messed up, as you mention

* it's not very easy to leaf through an ebook and to quickly jump from section to section

That said, I still read 90% of my course materials on my Kindle, Kindle app for OS X or Mendeley. For all its disadvantages, having a digital overview of all of your annotations is a godsend when doing research or studying for an exam.

For that same reason, I don't take paper notes anymore: while convenient, often they get lost, you can't search through them and you can't edit them.