Extremely vague question, since you didn't say anything about the conditions in which you plan to shoot. I shoot mostly with single flash (on camera). Don't be so concerned about the sweet spot of your lens...fill/ambient light is where you should have the most concern since you are only shooting with one flash.
Hopefully you have some control of the environment. Outdoors is preferred if you're not working in a studio, but you may want to have a UV and ND filter handy. (depending on location) If you have to come inside AND you don't have professional lights, then plan to shoot during the day, open the shades, and fill out the rest with daylight temperature bulbs. (turn off every damn incandescent or florescent bulb)
If you are shooting inside and have reasonably white walls, remove the lightsphere and point your speedlight directly behind you. It will fill quite nicely. (depending on room size and your flash power)
Try to avoid a situation where you are inside at night (or daytime with no exterior windows) unless you have some powerful fill lighting. (unless you are doing low key type work)