Putting in fonts is part of the problem. Part of my editing is to take out any coded-in fonts so that my Kobo reader can do its thing.
Simple is the key...no huge titles, no huge margins, no fancy anything.
I've gotten really good at making simple CSS in books using the #Calibre editor.
I also edit the html. For example, some long bit that is, say, a flashback and all in italics...man, that long italics has to go!
Ereaders often mess up on fancy stuff anyway.