The reason some PDFs are hard to read is due to the PDF file's content and the screen size (pixels) of the ereader.
PDFs that make extensive use of real text are much easier to view correctly, regardless of screen size. The font changes size according to the settings of the ereader.
However, many old PDFs used images extensively for things like special fonts or to create a specific page layout. In effect they are a series of pictures on a page, without "real" text even if there is writing present. It's just a picture of text.
This is where the screen size and resolution (pixels) come in. Graphics of any kind are dependent on the number of pixels used during creation. If the book has a fancy capital letter A drop-cap and you try reading it on a small screen ereader, you won't see the full letter A. What you will see is a portion of the A and then you will have to move the page around to see the rest - kind of like you had zoomed way, way in.
While moving the page around is not hard, it tends to break your concentration and the immersion factor of the book. Because you have to constantly fiddle with the device to see "all" of what you're reading. This is particularly true for any book that is graphics heavy: art books, roleplaying games, comics, manga, etc. However this can affect almost any book because their is no way to know how the publisher / maker created the file. Whether as text or as a series of images.
Again, older PDFs are more likely to make use of graphics; the PDF format has changed over time, becoming more ebook friendly although even today it is not perfect. On the other hand, ebook formats suffer from the opposite problem - they are not particularly graphics friendly.
In some respects it is almost better to have ebook formats for fiction and PDFs for any graphics-heavy publications.