While I doubt DNF will appear at E3 and 3dr's stance is pretty clear on the issue(re: attending E3s), it would absolutely be the most talked about/hyped/exciting announcement at the show, bar none.
Thinking about it more, if there really is hope DNF is being worked on/finished up.....E3 *SHOULD* be the venue that Duke Nukem comes back to with a
vengeance. He needs to remind everyone who the "original" alien ass kicker is.