On the plus side they're all marked NW/NE/SW/SE, but it's an occasional tourist mistake that can land a person way off course.
Even with a GPS, DC can be hard to navigate because there are so many discrepancies between most map databases and the actual streets. For example, I have a relatively recent Garmin, and every time I'm in DC it tries at least once to turn me the wrong way down a one-way street, or tries to send me down a street that isn't there. The one-way streets aren't alternated logically like the ones in NW Portland, either; there may be some rhyme or reason to the one-ways, but I have yet to decipher it. Another experience I often have in DC: a street I'm on suddenly becomes one-way in the opposite direction.
The craziest thing is that we have lanes and even whole streets that change DIRECTION depending on the time of day/day of the week.