How do you defend one of the most notorious terrorist figures in history? One step, legal analysts say, may be to ask for a change of venue.

Khalid Shaikh Mohammed’s lawyers, whoever they are, will no doubt question whether he can get a fair trial from a jury sitting, as Attorney General Eric H. Holder Jr. noted, in a Manhattan courthouse “just blocks away from where the Twin Towers once stood.”

Then will come the inevitable challenges to interrogation methods used on Mr. Mohammed during more than six years in detention. The government has acknowledged waterboarding him 183 times to extract information about the Sept. 11 attacks, which he eventually admitted planning.