Posit for example the sickle-cell mutation. Great for resisting malaria. And yet it is a single-nucleotide polymorhphism: even if both parents are "carriers" (have one gene for it, one normal gene), there is only a 1-in-4 chance a child will have the disease.
What is the timing of when the sickle-cell mutation began and (as it were) became "established" in the human population, compared to when Malaria first began infecting people?
Or, going the other direction, sometimes the environment changes and mayhap the genetics will need some time to catch up :
squirrels zigzag across the road, which is great for avoiding larger, less sure-footed predators, but not so good at avoiding being smushed under tires.
And yet we see no tendency of squirrels to avoid zig-zagging.
Is the "selection pressure" not great enough? Or has not enough time passed?
I think one of the biggest issues to be investigated in evolution, is comparing the rate of environmental changes to the rate of mutations;
and a better characterization for "sensitivity analysis" between a given "unit" of environmental change and the expected/"required" genetic changes.
(Wouldn't it be likely, as organisms grow more complex, that there would be different evolutionary clocks, dependent both on the system and/or organism, and the rate of change of the environment? -- e.g. horseshoe crabs and sharks are pretty much unchanged, as far as we know, over 200 million years; but Smilodon died out with the most recent ice ages, being a flash in the pan of maybe 2-3 million years.
But how many generations did it take to grow those way cool fangs, what specifically favored them over normal sized choppers, and how much selection pressure must have been exerted -- or lack of a barrier -- to allow them those canines to grow to the proportions they did?)