It depends, but you should do it, just to be safe.
Let's say you live in a town with one main road. The town council has decided that every road that has an intersection with this main road must have a stop sign placed on it. The idea catches on among the townspeople, and after the signs are placed accordingly, the accident rate goes down, and everyone is satisfied. Even out-of-towners catch to the pattern pretty quickly.
One day, you - a law-abiding citizen of the town - drive down a side street towards the main road. The stop sign is no longer visible because of all of the kudzu on it. It's nearly impossible to tell that there's anything there besides a lot of kudzu.
You ignore the stop sign and go out into the main road, in full sight of everyone, including a police officer. The officer charges you with a moving violation for not stopping at the stop sign. You argue against this, saying that the sign could not be seen.
The case - assuming you challenge the officer's decision - could rest on mistake of fact. Basically, if you had reasonable cause to not think that there was a stop sign there, the charges could be dropped, because there was nothing there alluding to the sign's existence. However, in this situation, such a defense would not be legitimate, because given how obvious and widely-known the policy is, there's no reason why you would think that a stop sign would not be there.
Each situation differs. A solid defense uses the concept of mistake of fact. If a sign was placed somewhere designating that cars have to slow down within that area (for some unclear reason), and the sign was not easily visible - or recognizable at all - then perhaps the defense could be used, because there would be no reason to think that there would be a sign there.
In short, it varies. The scenarios differ in each case, so there's no overarching policy.