Complete list of mistakes in the design of CSS: https://developer.mozilla.org/en-US/docs/Web/CSS/Reference

Just kidding. To me the biggest mistake was the standards' slowness in the early 2010s to provide badly needed new functionality such as a proper replacement for table layout, vertical alignment, etc. The cult of knowing specific tricks to get things working properly carried on for too long and made a lot of people annoyed at the semantic web (rip).