In my previous comment I said I couldn't even get it to start. Please ignore that comment, because on a new machine with a fresh install I have no problems. Although I think I did everything the same, I suspect my previous machine had either permissions, or its PATH, screwed up.

WU-Blast works very well, is immensely configurable, and is fast and accurate. It's not aimed at beginners, either with computers or with genetics in general. Although it's MacOSX native it's a UNIX program, purely command-line. The documentation is extensive but technical -- you're expected to have a general grasp of the concepts before you start.

I'm giving it four stars overall, because five stars implies that it couldn't be improved. I think documentation could be made more accessible, and installation and running could in principle be simplified. However, for the audience this is aimed at these are not really flaws. Technically WU BLAST does exactly what it should do, and does so very well.