I recently purchased a 430EX and still have basically no idea what im doing 
After reading a considerable amount of online tutorials etc I determined:
Indoors (when flash is the only descent light):
Manual mode, 1/200, pick a suitable aperture, ISO100. The ETTL will work out the correct exposure for you. If the green light on the flash doesn't show (and the photo is obviously underexposed) then the flash can't keep up. So pick a higher ISO, or lower F-value. (slower shutter won't make any difference)
Outdoors, or when you want fill-flash:
AV mode (or Tv), meter on the background. Shoot. If the person your trying to fill-flash with is too bright or dark, then adjust the flash-exposure-comp (either on the flash itself, or the camera)
The bit that threw me, is that using manual mode when using a flash is NOT the same as normally using manual. Using M for normal outdoor shooting you have to work out the correct exposure yourself. When using M with a flash, the E-TTL works out exposure, you just tell the camera a few starting settings, and it makes sure there is enough light.