Captcha images are quite effective at halting comment spam. However, besides being inherently inaccessible, they're also quite annoying to regular users.
How to maintain a spam-free site, without annoying your users? That's the question.
One idea would be to make the captcha-generating code more intelligent. The NP_Captcha Nucleus plugin already does this in a limited way, by not generating challenges for registered site members. But that's only a start. There are a lot of possible tweaks.
How about never displaying the captcha challenge immediately? After the user hits the submit button, a set of rules (blacklist, heuristics, ...) could be used to identify a comment as "likely being spam". Only in such a case, the user would be presented with an actual captcha challenge:
Result: in most cases, a user can post comments without interference of any kind. Only when a message has spam-like characteristics, an extra step is required.
How about the visually impaired, I hear you ask? The captcha should be accompagnied by an alternative audio-challenge. The challenge for developers here is to make such an audio file as good in telling computers and humans apart as a visual captcha. One site where I saw an audio captcha in action was the Passport registration wizard.
By the way, the same technique could be applied without the captcha. If the post looks like spam, the user could be allowed to fine-tune it, rather than dropping the post immediately. This is something which has annoyed me in NP_Blacklist in the past: a valid comment was seen as spam, a redirect to the spamtrap page occurred, and hitting the back button returned to an empty comment form :(
Just a bunch of thoughts...