I think trying to focus on all of the little details is distracting. I've sort of specialized in GMing city games over the years, playing in Sigil, a few home-brewed cities (from low to high fantasy) and quite a lot of sci-fi cities, including Coruscant (a planet-sized city) and some of my own creation for my OMEN system.
I get organized in an "inside-out" method, focusing on the areas that the party will be traveling in or around. You don't need everything memorized, but the more familiar you are with each area the better you can kind of create things on the fly.
I prefer to focus more on the people and the more significant set pieces than every little street and alley. If it isn't crucially important, then the width of every alley doesn't need to be elaborated upon.
Developing your own or familiarizing yourself with existing factions, social goals, political groups, illegal groups, and key people are more important than knowing the perfect layout of the city. I usually make a faction chart in photoshop with the names and a one line blurb of what they are, and then draw different types of lines to the different factions. A red line connecting to a faction is an enemy, blue line is neutral, and a green line is an ally.
Once you become familiar with everything, pretty quickly plots and hooks will develop around certain factions. For example in my current campaign, the party is playing on a gigantic space station with over 20 million in population (I know, really big, I get it) but 18 major factions. The party has been hired as a crew of third-party contractor/specialists in their respective fields to help mitigate a growing violence problem in a certain sector of the station, which some of the PCs have a personal connection to the area.
Have I detailed every sector in the entire station? No. Do I have pages and pages and pages of information on every NPC they might meet? No. I build things locally around the PCs interest, and since we usually only game 4-6 hours, I don't have to go too crazy with expanding their influence. Since I understand the 18 factions pretty well (I've created all of them myself) and their influence upon and with one another, I can kind of use place-holder NPCs which represent that faction as opposed to making an interesting NPC for every single street corner.
So, to break it down:
- Familiarize yourself with the key, important parts of the city
- Create or know all of the factions (even the smaller ones)
- Create a few named, significant NPCs that the party will interact with immediately
- Focus on the "inside-out" local area that the party is likely to operate within
- Don't memorize every detail of every street, keeping it nebulous is fine for most players and easier on you
- Try to develop a "feel" for each neighborhood or area within the city, if you watch Game of Thrones, this show does a very admirable job at making every location have an obviously different atmosphere, color scheme, weather, etc. You can do this in neighborhoods in a city (just like Uptown NYC looks different than Brooklyn.)
Have fun and I'm sure you guys will love operating in a big city.