With manual flash, you have two separate exposures you'll have to set and balance - background exposure and subject exposure (illuminated by flash). Both are affected by aperture and ISO, while only background exposure is affected by shutter speed and only subject exposure is affected by flash power setting.
First, you'll set your aperture, ISO and shutter speed so that depth of field and background exposure is like you want them to be. For getting more accent on your subject, you might want to underexpose background by a stop or two. With digital, it's easy to confirm the exposure by taking a test shot (flash powered off) and studying the histogram. For most efficient flash power usage, your shutter speed would be equal to your camera's sync speed (for a 5D mark II, 1/200 s according to specs, but that often causes a dark band with flash, 1/160 would be safer). Using high-speed sync is rarely a good idea.
Next, you'll adjust flash exposure by setting your flash power to a guessed approximate value (don't worry, you'll get a feel for setting the initial power after you've done this a few times) and pop another test shot. Adjust flash power to get the exposure you like and voilà!
With multiple flashes, you'll adjust power for each flash one after another.
As you can see, operating a flash in manual mode is a bit time-consuming, not very well suited for "capturing the moment" or moving around a lot. That's what you have TTL for. Manual flash is for when you sculpt out an image the way you want it to be. Therefore, Av mode may feel awkward with manual flash (you don't have control over shutter speed to control background exposure) and M mode might be better suited.