The "obvious" difficulties that everyone recognises:
Firstly, what do I mean by difficulties? For the purposes of this discussion, a difficulty is something that makes poorly designed Web content hard - or impossible - to use. Have a look at the introduction to WCAG10 - the "They May" list there is a list of difficulties.
The most obvious difficulties, and the ones that sadly are often considered to be the only ones that need to be addressed, are things that affect someone's ability to use a "normal" user interface - for a given value of "normal", probably defined by someone working in Redmond, Washington.
It is generally accepted that there are people who may not be able to see a screen well or at all, may not be able to use a mouse and/or keyboard. I would like to say that most supposedly accessible design that I have encountered covers these very basic issues, although I find that ease of keyboard navigation is often poor.
Moving on - this is not a discussion on general accessibility, just setting the scene. Next slide please, maestro.