When a client demands that my designs be identical in all browsers and across all platforms. One of my first jobs when I started doing design/dev professionally was for a fellow who couldn’t deal with the fact that a piece of text using a web-safe font would break lines at different words depending on the platform.
As a side note, this is one of the reasons why I love responsive design. It forces the client to accept that the website is a flexible being, and that user experience comes above pixel perfection.