That depends entirely on what you call minor. A lot of people on HN think that it's absolutely essential that a page loads and responds within a few milliseconds, because somehow subconsciously to users, it will make the site feel snappier, and thus better, and thus more worth paying for / sticking around on.

Compiling and running LESS on the fly in production might, besides the extended load time, increase the chances for a flash of unstyled content. If this makes you nervous, don't run LESS on the fly in production.

Not to mention if you run it on the fly, the "flash" of unstyled content will last forever for people with JavaScript disabled!