A couple of good suggestions so far. To, hopefully, add some further points...
The seawall is a walkway that encircles Stanley Park, along which the 9 o'clock gun sits. Although the gun is across the bay from the city, depending on the location of your accommodations, walking to the gun can take quite awhile. As an example, from Georgia and Granville area (right downtown), it is probably close to an hour, so a taxi or bus part of the way may be an option. The last time (couple months ago) I was there, the gun was not lit. Not sure if it is lit all year round or only at a certain time of night. A couple hundred feet from the gun is the statue of Harry Jerome, which can make a nice foreground silhouette (search for one of my images from a couple months ago - shot with a 100mm lens). From the seawall, you can use anything from a wide angle up to about a 150mm, depending how much of the city you want to capture.
Farther along the seawall (another 5 minute walk from the gun) is Brockton Point Lighthouse, however, it is blocked from the city by a stand of trees and, even if the trees were absent, to get it in the foreground of a city shot, you would have to be out in the water. Having said that, you can include it in the foreground of a shot across the water to North Vancouver, or I also think it can be included in a shot of Lions Gate Bridge. Keep in mind, it is not necessarily a classic lighthouse. It is quite small and the light (if it has a light at all) does not rotate.
False Creek is also an excellent location to get a city skyline and from there you can get the city as well as the sports stadium (lots of changing and colourful lighting) with Grouse Mountain in the background. If you have a wide enough lens you could also include the Science Centre (big round lit up ball). Once again, depending on how much you wish to include, you could use a wide angle up to about 150mm.
The above two locations will ensure an image that includes a lot of the city's business and residential high-rises. From the other side (near the planetarium) you are mostly faced with residential high-rises, with the Burrard Bridge off to your right (Granville Island and marinas are just past this bridge. I've never found real good photos of the city from that side, unless you venture further west to Spanish Banks (a few miles away, almost to UBC).
As to safety, it's a big city with big city problems but in all the times (dozens and dozens) of times I have been out, both late night and early morning, I have never met with problems. Of course, there are places you should not venture by yourself and with camera equipment.
As you didn't mention how many nights you will have for shooting, if I had only a single night, I would probably concentrate on the city from the Stanley Park seawall. It's the location for iconic city skyline. If more than one night, I would then consider False Creek.
There are a bunch of other locations of photographic interest, so if you wish more detailed stuff and some sample shots (with exact locations and how to get there), pm me your e-mail and I will provide more and answer any questions you may have.