While I am of the opinion that the best way to really understand and enjoy a neighborhood is on foot, the 22 Fillmore bus does a pretty good job of summarizing what Potrero Hill has to offer. The 22 bus starts off in the Marina, winds through the Fillmore (including the renovated part) and Mission. Then, it ends up on the western side of Potrero Hill and takes you up and down to the eastern side.
As the bus zig and zigs through the neighborhood, you start off at Potrero Center, one-stop shopping, with free parking The bus passes the UPS pick-up facility (we all have to go there at some point in our life) and then takes you past the Whole Foods, and some independently-owned businesses along the flat part of Potrero. Then, the 22 bus climbs to the restaurants and cafes of Potrero Hill, along 17th and 18th streets, and gives you a glimpse of the Bay before ending at 20th and Third streets in the Dogpatch neighborhood.
The 22 bus is truly one of the magnificent rides in San Francisco. Very few other buses take you through so many interesting neighborhoods with so many interesting characters. It offer a great summary of what Potrero Hill has to offer on foot.