Pokeweed narrowly beats out Giant Hogweed for me, because I've not only encountered it but I've had the supreme misfortune of having to remove six of them from my yard (counting young ones). Plus I'm pretty sure it's going to return, as each plant produces tens of thousands of seeds (and two yards in my area also have Pokeweed present).

"This plant is a poisonous weed and can cause severe poisoning in humans. All parts of this plant contain saponins, oxalates, and phytolacine. However, the roots and seeds contain the highest concentrations of these toxins. Severe cases of poisoning result in purging, spasms, and sometimes convulsions."