Favor open formats that represent a technological least common denominator, and degrade gracefully.
With consideration of the wide variety of assistive technologies in use, and the wide ranges of disabilities, any solution that aims to target a specific segment of users is short sighted. Rather than attempt to address every assistive technology, and every disability, a general approach consisting of open formats, graceful degradability, and alternative formats (including "least common denominator" formats such as plain text), alongside common sense approaches to accessible design are best.
Open formats are the first layer of accessbility. By making sure that a wide variety of applications can be used to access information, you increase the chances that a given user will be able to find a way to use it, regardless of their access to any particular assistive technology or their disability.
Graceful degradability is another key. This is a key part of the way the web is intended to work, that has been lost in an era of "Web 2.0" and ubitious use of Flash animation. To put it simply, it means designing for the lowest common denominator technogically, and building up incrementally from there to the most advanced for which support is desired, in such a way that if any of the technological features beyond the lowest common denominator aren't there, the content is still presented in the best way practical. This may sound complicated, but, with foresight and common sense, and a "ground up" approach, it's not signifigantly more difficult than just writing a web page. HTML was actually designed from the beginning for this approach, as are several complementary technologies.
Least common denominator formats, such as plain text, CSV, and HTML are desireable as alternative and/or primary formats for information because of broad compatability and openness. These formats can be easily fed to a broad variety of assistive technologies, and HTML has the important property of graceful degradability (assuming proper design) when presenting multimedia content.
Common sense accessible design approaches are also very much necessary. That means at least a general awareness of good and bad design habits and the broad spectrum of disabilities such as blindness (partial, total and color), deafness, and mental disabilities. The section 508 guidelines provide extensive guidance, but some basic principles such as making sure the information is available in a textual form, and making sure that stylistic considerations such as text size or colors aren't implemented in a way that they become binding on the user can resolve a majority of issues.
Single source publishing is also a novel approach to improving openness and accessability without signifigantly increasing the cost or difficulty of publishing information. With a single source publishing technology, content is authored in an intermediary format, usually in a semantic markup language such as Docbook. The use of a semantic markup allows a consistant conversion to a broad range of final formats, and insures as much of the structure and content of the original document as possible makes it into the published forms, while shifting most of the accessibility-sensitive design work away from the creation and authoring of content.