I'd say get a good general feel for the city's atmosphere (like Jester suggested, great stuff there, man!), but also prepare some specific places that are likely to be sought out. You can fill in bits and pieces of atmospheric stuff here and there, when you describe other things.
For example, a fight in a dark alley could start with you saying: "You seem to have taken a wrong turn. Like most of the city, this street is lined in whitewashed wattle-and-daub houses, but here, they seem uninhabited, in bad repair, with windows boarded up and doors barred. Around the next corner, you hear excited whispers, which quickly fades as you approach...".
A quest providing merchant's mansion could be described like this: "After crossing the poorer parts of town, where people live in five- or six-storied buildings which lean toward each other over the streets, barely letting in light, this seems to be a much more well-off quarter. Your host resides in an elegant villa, only two stories high, with a tiled roof and paned windows, surrounded by a flower-filled garden complete with fountains."
In a city dependent on fishing, a slight smell of fish permeates everything and can be mentioned on occasion. At dusk, the last light of the sun reflects off the bay, and the crying of gulls fills the air.
In a city dependent on lumber, the smell is that of resin and tar, the sound that of giant sawmills. In a city famous for its three knightly orders, the sound is that of weapons clanging in the practice yard or of bells calling to mass, and the last light of the sun reflects off the arms and armor of a patrol passing on the city walls. Etc.
For many places which cater to adventurers, you only need one description, even if there are many such places in town. For example, you can normally come up with just one description of an inn and use that for the inn the players choose for their PCs. However, it's nice to have a few inns' names at hand, as well, to leave the illusion of choice to the players:
"So, you guys probably need to hole up somewhere, and there're a few places right behind the gates that seem to cater to your kind of clientele: well-traveled, weary, and not as wealthy as you'd like. The Golden Griffon seems rather uppity-upper-class, and the Hole in the Wall seems to be just that, but the Dented Helm has a cozy, trusty feeling at first glance, with a few... rather adventurous-looking folk sitting on the porch, and a buxom tavern wench serving ale from a pitcher. Where do you wanna go?"
9 times out of 10, the Dented Helm it will be, so prepare a tavern under that name, add a few idiosyncratic details (a huge, dented, Fire Giant's helm hanging from the ceiling; the buxom wench is a Changeling and alters her appearance by what she judges menfolk she's serving will probably like; a chimney system going through each room provides warmth in winter and carries sound rather well; etc.), and you're done. Should the PCs choose another inn, just replace the namesake element. For example, if the PCs ignore the Dented Helm and explore the city first, finally deciding to take room and board at the Singer's Repose, you put a small stage in the taproom and don't put a Giant's helmet there. Simple.
Similarly, you probably want a weaponsmith and whatever passes for a provider of magic items in your campaign (dependent on power level). You will hopefully know what your group is usually on the lookout for, right? Make up one place each. Don't dwell on the details too long - your players will want to buy and sell, not gape at the scenery.
So what it all comes down to is modular description: you don't need too many fleshed-out descriptions all ready and made up. Instead you want recurring elements, which you can use in many other cities as well, but fill in the blanks with the individual atmosphere you want to convey. In another city, the Dented Helm is called Minotaur's Munitions and sports a huge broken catapult. The gruff Dwarven smith who constantly grumbles about the weather even though he never leaves his anvil is a gruff Human smith who constantly grumbles about his wife even though she's three years dead. The crazy Half-Elven wand seller with a nervous tic and strange hair is a slightly-too-polite Gnome potion seller with a straying eye and strange hat. The corrupt city guards are corrupt customs officials. And so on.
To flesh out the uniqueness of a city, on the other hand, you want one or two things that are iconic for it: crafts & industry, culture, unique buildings etc. Lots of forges, foundries, and smithies is a nice suggestion (I've used this before, actually); or in the case of Scornubel, a river harbor with dozens of small fishing craft and a few gilded pleasure barges for the well-to-do; maybe a huge alchemist's guild in the center of town, with lots of space around it on all sides where nobody dares to build. I like to put a renowned theater or conservatory in some places. Or maybe there's just a lot of street artists wandering about, freaking out the foreigners. Sculpture could be 'the thing', as well, with all the rich people decorating their homes and gardens with statuary, and public spaces regularly crowded with it.
For places, how about strange and wondrous architecture like a rose-tinted glass tower, an iron palace with gates forged from swords, or an elven-grown giant tree with small shops in its trunk and boughs? How about a bottomless pit with swingy walkways across where condemned criminals must fight till one of the falls? Or just a regular old bazaar with exotic spices, foreign fashions, live Owlbear cubs (chicks?), and of course lots of haggling.
Pick one each and go with that: just one industrial or cultural "specialty" is probably enough; adding one "unique site", which is independent of the "specialty", gives the city a less one-dimensional quality. Adding on more stuff is pretty unnecessary for now and will probably even detract from the city's memorability.
Furthermore, and most importantly, the city needs a reason to be there from a plot perspective. What's going to happen within the city? Who is going to approach the PCs about that sinister cult that seems to recruit so heavily of late? Will the Thieves' Guild make an attempt on a PC's life (or just his hard-earned phat lootz)? Is there a murder plot in the city's high society, and is the Elven emissary involved? Or is there a Wererat problem in the slums?
These are the things that you're including the city in your game for - so these need to be fleshed out beforehand. It'll be best to have two plot hooks ready, so you can spring one on your group when it's convenient during their shopping/recreation (and use the other one in the next city, or here but at a later date).
Wow, it's late. Hope I could help.
