I am using a default font size of 26px and stackoverflow's layout seems to not work well with such a large sizes.
The most important issue is that many inputs tend to overflow and partially get hidden below side text. This includes one with login, ‘Title’ and — the most important issue — the editor, which makes writing posts a little painful.
Another important one is that sometimes 'search' field doesn't fit in topbar and jumps lower, being partially hidden by logo. I met that issue on stackoverflow itself only while serverfault & meta display fine (but that may be related to rep or sth).
There's one minor issue too — navbar is too narrow and ‘Ask Question’ jumps below — but this one looks quite nice (maybe it's even intended?).
Screenshot: (click to enlarge)