Opener Warner has managed just one hundred in more than three years in the longest format but was retained for the World Test Championship final against India next month and the first two Ashes matches.
Former England captain Vaughan said Australia, who won 4-0 at home in the last Ashes series in 2021/22, should consider having Mitchell Marsh open with Khawaja.
"Why would you want to throw out two lefthanders to Broad and Anderson?" Vaughan, who helped England end their 18-year Ashes drought in 2005, told the Sydney Morning Herald.
"... looking at the way that those two bowl at lefthanders, particularly in English conditions, why would you give those two great bowlers exactly what they want at the top of the order to get themselves up and running?"
Vaughan added that Marsh's ability to bowl a few overs made him a good option.
"I would honestly look at someone like Mitchell Marsh to open the batting because it gets him in the team. He's done all right against England."
Vaughan said there could still be a place for Warner lower down in the order.
"The one thing with David Warner, I know England fear him,” Vaughan said.
"He's such a good player when the ball that's not moving. The ball won’t move after 30-odd overs in English conditions. Could they find a place for him at five or six?
"I wouldn’t be against looking at him down in the middle of the order to get him in the team because I think (what) others will want is his kind of tenacity and his mentality and his aggressive way."
The five-test Ashes series begins at Edgbaston on June 16.
