The Historic Quarter of the Seaport City of Valparaiso is both overwhelming (from a traffic perspective) and underwhelming (just looks like a shabby port city) at first - until you go up!  However you choose to get there - drive, walk, bus, funicular - just go up. It is one of the most visually stimulating cities that I have ever visited.

A good way to understand the Historic Quarter is on Cerro Concepcion - especially around the Casa Patrimonial area where you can see tons of historic houses indicative of the historic period of the late 19th century while also looking out onto the historic port.  

Although the murals of "Valpo" are not technically part of the World Heritage site, they are a must to visit and are located throughout the historic area.  There are many tours that focus specifically on the colorful murals but you are guaranteed to stumble upon some of them by simply wandering the hills of Cerro Concepcion and Cerro Alegre. 

It is very easy to get to Valparaiso by bus from Santiago (the city or the airport) in about 90 minutes.  You can also drive - but beware - it's the first city that ever nearly got the best of me.  Google maps doesn't work well because the hills of the city are so vertical that GPS doesn't work well.  Also, the streets are generally not marked. Parking is also a challenge.

Valparaiso is considered to be somewhat unsafe at night and the port area is definitely "seedy".  A good alternative to staying in Valpo is to visit the beach town of Viña del Mar just 10km north.  Viña del Mar has a nice beach, a wide-range of places to stay, great restaurants, including The Waterfront Restaurant and easy access to Valparaiso.