Good day!
I hate driving in cities. With a vengeance. With the fiery hated of a thousand suns.
In particular, I hate driving in Denver, mostly because I live there.

Anyway, I feel like I've got a pretty good handle on the ins and outs of getting around this fair city we've got going, so I thought I'd give a quick overview of the dos and donts, as well as the birds and bees of city driving. (I feel dirty after writing that)

I realize not everyone lives in the Mile High city (though it seems like they do), but I hope that this instructable will inspire others to create similar guides for their metropolitan/urban areas of their choice.

Step 1: Geography and Street Layout

First off, the most important thing for any driver is knowing where you are in relation to your destination. The best way to know where you're at is to know which way is north (or south)
Luckily, we here in Denver are the noble decendants of those intrepid explorers who came west on wagons, saw the mountains, and said "Screw it, we're here!"

The Rocky Mountains are to the west. This is easily the most helpful advice anyone ever could get for driving here.
The mountains can also be seen from pretty much anywhere in Denver, and once you've got a handle on that, you can find your way north or south, because anywhere is better than where you're at right now, which is, inexplicably, Denver.

Another helpful fun fact: 90% of the roads here run on a grid, meaning north-south, or east-west. The only areas this doesn't apply are downtown and in the suburbs (places like Littleton and Highlands Ranch, but what are you doing there?)
The streets in Downtown Denver are on a angle, they run northwest-southeast and vice versa. The reason for this is ingenious: in winter, all the streets will get a good 3-4 hours of sunlight, which would melt the snow! Brilliant! Except when it really snows (like four or five feet, which is rare), it's never sunny! Wheeee....

Step 2: Cities and Areas

In common conversation, "Denver" could refer to many things.
The City of Denver,
The County of Denver,
The Denver Metro Area,
The Denver Omelet,
John Denver....
...I can't help you if you're trying to drive a Denver omelet,and I don't think John gets around much anymore...

In reality, there are 20 or so adjacent cities that make up the "Denver Metro Area", which is what most people use to refer to, um, the denver metro area.
A nifty map with all the cities is below, but I'll outline the most common ones:

Downtown: Slang for the City of Denver, which encompasses all the big skyscrapers and sports teams; the center of all that is Colorado
Lakewood: The west side of town; the biggest city gets the naming convention. Populous.
Aurora: Conversely, the east side of town. Shady folk here.
Wheat Ridge/Arvada: Northwest Denver, mostly residential, except when it's not.
Littleton: Southwest Denver, suburbs and Lockheed Martin MI complex; stay away unless you have a missile to sell.
The Tech Center: Included: Englewood, Centennial, and Highlands Ranch; Straight south down I-25, headquarters and branches of seemingly every white collar corporation ever, and the mother source of all of Denver's rush hour traffic. Seriously.
Westminster: Like Arvada North, except, well, it's Arvada North.

Also notable:
Golden and Morrison: Make up the far west and southwest edges of The DMA, very nice little towns, except for the foul monstrosity of the Coors plant. (Red Rocks is in Morrison, though, so it balances out)
Boulder: Far far away up to the Northwest, everyone should know where Boulder is so they can avoid it like the plague, unless it's April 20th.
Castle Rock: Surprisingly Stephen King free, CR is in between Denver and Colorado Springs, and has a rock that is apparently heavily fortified. Detour around if unarmed.

If you're new in town, you'll probably have experience with the airport, which is currently Denver International (there's been like twenty airports in the last 50 years, whatever.)
DIA is kind of interesting, it sits 40 miles northeast of downtown, but the city bought up all the land along I70 and now the city and county of Denver extends wayy on up, for some reason. DIA is actually pretty nice, considering it sits in the middle of a cornfield and is shaped like a swastika...

Step 3: Interstate and Highways

If you are simply passing through Denver on your way to more exotic locales (like Omaha), consider this the only step that affects you.

Looking at a map of Denver, the first image that springs to mind is that of a hamburger. Actually I'm just hungry and really Denver looks more like a crosshair from above.

There are two major Interstates that cross here, around these Denver has sort of coagulated. I70 carries your east-west traffic, and I25 is north south. Both of these cross most of the country and run for hundreds of miles, so they're my logical starting place, since you'll be using them most often. For when you arrive, and when you flee.
There's also I-76 and I-270 directly north of downtown, they cross at I-25, and are pretty much useless for in-city driving.
On the Southern half of the crosshair, C-470 and I-225 create a big loop that acts as a city wall, keeping the heathen tribes of the suburbs out at night.

For intra-city travel, there's highway 285 on the south half of the city, it runs from I25 west and then south, and eventually will take you into the mountains and to freedom. It's a good choice for avoiding C470 at busy times, but there's currently (meaning forever, in Den-speak) a lot of construction, so it's not always the best.
The northern equivalent is 6th Avenue, or Highway 6, turns from a one way street into a highway and will also lead you into the mountains, intersecting both I70 and C470 along the way. It's peachy, most days.

For residents of Denver, consider this: the Denver Metro area covers 8500 square miles, making Highway and Interstate use almost inevitable. HOWEVER, that does not mean that a 6 lanes road will get you there quicker than a two lane one. (size doesn't matter)
It's all about playing the time game, and knowing when particular routes are shitfucked during the day.

Step 4: Taking the High Roads

OK, on to the (ground) meat.

Like I said earlier, the most important thing to remember about driving here is knowing what routes are clogged, at what time of day, and when to ignore your GPS.

For example, if your GeepeySauce or mapagoogles or whatever the kids are using these days tells you to take I25 through the tech center, at any time, on any day, I would counter it's instructions with an offer to chuck it out the window for you. I25 is always hosed, and there's nothing to be done about it by you.

Aside from the highway of death, the time of day matters most when using I-70 or one of the other major highways.
Example: because of the way the 303's laid out, most people live in the west or southwest, and drive north east or east to get to work, and vice versa on the way home. So, logically, avoid I-70, 6th ave, 285, and C470 eastbound until about 9:30 or 10am, and westbound from about 4-6:30.
Easy enough right? WRONG. NEXT STEP.

Step 5: Back Down to Earth

If you're avoiding the highways, you'll be using surface streets to get around. The problem with that is that then you have to deal with the increased traffic that comes with driving near shopping centers, or parts of town that are heavy on business.
I unfortunately can't speak on all of the major streets in Denver, but i can give you an example with the streets I live near:
Wadsworth blvd is the most direct route for me to get home from 6th ave, but Wadsworth is almost 100% commercial property from 6th to C470. that means that all the soccer moms going to Garts, all the hipsters ironically shopping at Walmart, all the Honda Civics with $400 rims and junkyard doors, they all use this road, and they all drive like idiots (more on that later)
But wait! Kipling Street has nothing but homes and schools on it, and it's only 30 seconds farther up 6th avenue! But more importantly, there's a Dippin Dots on the way home! Yippees!
It's well-thought out decisions like these, made for the right reasons, that can make the difference between a blissful day of futuristic car friendly ice cream enlightenment and shitting in a 30 mile long parking lot filled with douchebags who aren't even douche-ey enough to honk at each other.

Step 6: Your Fellow Vehiculists

The best piece of advice I can give you about the other people on the road is that the sooner you realize that everyone else is either an idiot, an asshole, or legally blind in this town, the sooner you can make the decision to buy a bike, leave it at home, and ride the bus.

I realize that every city has it's share of bad drivers, but Denver's infestation is compounded by a couple of crucial elements. The first is what I assume must be Colorado's incredibly low age requirement to obtain a license (apparently 4 and a half, judging by the generally juvenile approach to basics like sharing, counting, and potty training), the second is what most people think of when they think of Denver: weather.
CONTRARY to popular belief, the Mile High City is not a mountain town, and 300 days of sun a year does not justify having streets at an angle. It snows here, yes, but infrequently, and never really enough to close schools, which is the only reliable weather predictor we have.
What comes with mild weather are mild drivers, which means that at the slightest sign of rain or snow or wind, people starts slamming on their brakes, running their windshield wipers, and generally driving like the apocalypse has broken out. Avoid these people (read: all people) in inclement weather, and pray to god that CDOT has its shit together this time.

A word on speed limits: Add 5. The fast left lane drives five above the limit, and the slow right lane drives five below. Or as fast as they can. The middle lane, therefore, is completely free to merge into one of the other lanes, since no one likes wafflers. Cops don't care unless you're endangering others, and the other drivers don't care because they're too busy eating/sleeping/drinking or writing instructables.

Step 7: Happy Trails

Well, this turned into a rant pretty quickly, didn't it?
Take it or leave it, just don't forget to avoid I25 and always make sure you wear a helmet, and you'll be fine-ish.
/Fultron