To failure, regardless of the number of reps per set.
Failure is relative to factors like using a spotter/workout partner, and your focus during a particular phase of training. You want to avoid injury, but you also need to push yourself beyond the limits of your mind and actually push your body (wisely).
Personally, I find that I need to prevent plateaus or peaks by focusing on alternating cylces (three to four weeks at a time) of sarcoplasmic hypertrophy (higher reps, endurance) and then myofibrillar hypertrophy (strength, low reps, heavier weights), but I ALWAYS work towards failure. That's what my body responds to.
To understand how either works - and I believe EVERYBODY who lifts seriously NEEDS to understand this, or you're wasting time - the best simple break down of it that I ever found is herehttp://skinnybulkup.com/hypertrophy/
Understand this, and understand what true high intensity heavy-duty training (a'la the late Mike Mentzer) is all about, and I think you'll be training in the smartest possible way. The rest is diet and rest. Period.