Incidentally, I just finished reading Knuth's original article from which his now famous quote originated. If you'll forgive the large copy and paste I think it is insightful to see the quote in context.
The original quote from 'Structured Programming with go to Statements' Computing Surveys, VOL 6, No. 4, December 1974 on page 268 is:
"The improvement in speed from Example 2 to Example 2a is only about 12%, and many people would pronounce that insignificant. The conventional wisdom shared by many of today's software engineers calls for ignoring efficiency in the small; but I believe this is simply an overreaction to the abuses they see being practiced by penny-wise-and-pound-foolish programmers, who can't debug or maintain their "optimized" programs. In established engineering disciplines a 12% improvement, easily obtained, is never considered marginal; and I believe the same viewpoint should prevail in software engineering. Of course I wouldn't bother making such optimizations on a one-shot job, but when it's a question of preparing quality programs, I don't want to restrict myself to tools that deny me such efficiencies.
There is no doubt that the grail of efficiency leads to abuse. Programmers waste enormous amounts of time thinking about, or worrying about, the speed of noncritical parts of their programs, and these attempts at efficiency actually have a strong negative impact when debugging and maintenance are considered. We should forget about small efficiencies, say about 97% of the time: premature optimization is the root of all evil.
Yet we should not pass up our opportunities in that critical 3%. A good programmer will not be lulled into complacency by such reasoning, he will be wise to look carefully at the critical code; but only after that code has been identified. It is often a mistake to make a priori judgments about what parts of a program really critical, since the universal experience of programmers who have been using measurement tools has been that their intuitive guesses fail. After working with such tools for seven years, I've become convinced that all compilers written from now on should be designed to provide all programmers with feedback indicating what parts of their programs are costing the most; indeed, this feedback should be supplied automatically unless it has been specifically turned off."