In TOS where, say our heroes seek to divert an asteroid heading toward a planet.
And in 100 years, that diverted asteroid destroys a different civilization.
The law of unintended consequences is a strong argument for the Prime Directive, IMHO.
Of course, the flip side is that simply being present changes things. Exploring, recording, taking samples of things...
If they really wanted to never interfere with anything, they'd never leave space dock.
It's truly complicated, and the times they explore those complications are better than simply declaring absolutes.