Try and write CSS code that is as simple as possible for others to reason about in future. Loops, mixins and functions should seldom be written. As a general rule, if there are less than 10 variations of a rule, write it by-hand. If on the other hand you need to create background positions for a sprite sheet of 30 images, this is something that tooling should be used for.

This pursuit of simplicity should be extended in the manner layouts are achieved. If a better supported layout mechanism achieves the same goal with the same amount of DOM nodes as a less well supported one, use the former. However, if a different layout mechanism reduces the number of DOM nodes needed or presents additional benefits yet is simply unfamiliar (for example Flexbox), take the time to understand the benefits it might offer.