Union Square is often the assembly point for big demonstrations.

And currently Trump Tower is the biggest destination point, although the Trump Int'l hotel on Columbus Circle has also seen some action.

When demonstrators have tried to disrupt traffic, they usually target big highways like the FDR or West Side Highway or bridges. The most recent big disruption was an oddball immigration activist group that chained themselves to the railings of the GWB a few weeks ago. But it's been a while (a year or two?) since I've heard of anybody trying to shut down the East River crossings.

As Blumie says, the subways are very unlikely to be disrupted so just know your public transit alternatives in case your car gets stuck in traffic.