14th Street
Everything south of this is considered to be "downtown". Meaning: the street grid falls apart, the proportion of hipsters to investment bankers increases substantially, and NYU students abound.
Union Square is located at the point that 14th meets Broadway and Park Avenue. One way to get there is to take the 1 train to 14th Street (or transfer at 96th to the 2 or 3 for the same station) and walk east along 14th.