The HTML parser in any email client is not nearly as sophisticated as a standard browser is. Better use HTML 4 markup to create/generate messages with HTML styling.
Also, if you think that browsers can be incompatible, because of different HTML/CSS interpretations, you have never tried to send out a HTML newsletter that looks the same in any mail client and/or web-based client like GMail or RoundCube.
You'd better keep it structurally simple, use (nested) tables instead of HTML5 and the least amount of CSS you can get away with. That does keep the layout of your generated HTML message more or less the same between different mail clients.
Yes, I'm fully aware on how the above sounds. Took me hours to design and generate HTML mail messages correctly (using Windows batch script, so you could say I learned this the hard way). Mail is received correctly in the Thunderbird mail client and GMail/RoundCube clients, around 99% of the content shows up correctly in Outlook 2010, Outlook 2013 shows about 95% of the content correctly. Never tried it with newer versions of Outlook.