If the purpose is to disrupt travel or commerce, it would most likely achieve it's goal almost immediately. If the purpose is to bring attention to some other issue and the disruption of the highway system is unrelated (or only tangentially related), then the attention would have to be weighed against the negative impression it creates for the many affected.
I don't have the relevant experience in this area to know under what circumstances protests that negatively impact average people succeed in their goals.
In a vehicle protest you forfeit anonymity (lincense plates), ability to split since road-blocks can easily stop you, and most importantly your vehicle might be impounded.
It's the worst. You're not demonstrating anything. You're just pissing off commuters.
I believe the culture is improving here, but for a long time, cars were such important symbol of wealth that being a pedestrian gained a small but real social stigma. Large cities that were already thriving and had very affluent people who didn't drive bucked the trend, but in your average city in the US, if you're on a street and not driving, you look poor, mentally unstable, or homeless.
I'm going to interpret that question literally. A key thing you have to keep in mind is that in almost all of the US outside of a few very large cities, the "street" is not a useful public place. People don't gather and interact on streets in the US. They are merely channels for cars. Protesting on the streets would be as useful in most cities in the US as wandering around next to a shipping lane on the open ocean. The only people "there" are driving vehicles at full speed.
That of course raises the question of where Americans do congregate together. Churches are the answer for many, although I believe those are dwindling. Some go to bars. Neither of those is a particularly good venue for dissent.
One unfortunate consequence of the US being so car-centric is that we've destroyed public space, and consequently made public assembly much harder.