But in Plaquemines Parish, just southeast of the city, three levees overtopped, creating a kind of flooding the parish did not see even during Hurricane Katrina, which hit seven years ago Wednesday.
"Now the Coast Guard's got to go out with winds still gusting 60 to 70 mph in some areas" to save them, she said.
The New Orleans levee system and pump stations were working furiously to deal with the deluge.
The system was rebuilt and reinforced at a cost of $14 billion after it failed when Katrina struck in 2005. Nearly 1,800 people died as a result of that storm, the majority when levees and flood walls failed and flooded.
Officials were considering intentionally breaching the levee downstream to allow some of the floodwater to flow back out of the inundated area, Jindal said.
Nungesser said his parish will need federal funds to rebuild. But first the searches continued.
"We are still looking for stranded residents," he said Wednesday evening. "We will resume a double check tomorrow on the homes on the east bank (of the Mississippi River). We're checking the west bank for anyone who may have been trapped."
Parish resident Gene Oddo told WWL that he was in his attic with his wife and 18-month-old baby girl.
He said the water was above his front door, and he did not expect it to reach the attic. But if it does, "I'm gonna have to shoot a hole in the attic to get up here on the roof."
His neighbors, including a 92-year-old man who refused to leave his home, were in a similar predicament, he said.
"People who went through Katrina are pretty nervous about storms, and large numbers of people have left," Lynn Magnuson, 58, said Tuesday in a CNN iReport.
Magnuson said the Lower 9th Ward, which was hard hit by Katrina, "is pretty empty right now."
About 1,000 National Guard troops and more than 2,900 law enforcement officers are in the city ready to address issues related to the storm, Mayor Landrieu said.
Isaac made its second landfall at about 2 a.m. CT near Port Fourchon, in southeast Louisiana 60 miles southeast of New Orleans, after slamming first into Plaquemines Parish along the coast and then wobbling back over the water near the mouth of the Mississippi River, the National Hurricane Center said in an early morning update.
In Biloxi, Mississippi, 50-year-old Alfonso Walker was keeping a close eye on the progress of the 195-mile-wide storm.
He watched as a storm surge sent waves crashing over the pier at the IP Biloxi Hotel & Casino.
"I went through Hurricane Camille in 1969 and Hurricane Katrina in 2005, where I lost everything, and every other hurricane in between those two that came through," he said in a CNN iReport.
"So I'm a little concerned."
Isaac could bring 14 inches of rain across the region, and as much as 20 inches in some areas, including parts of Louisiana, Mississippi and Alabama, the hurricane center had predicted.
The center of the storm "will move farther inland over Louisiana tonight and tomorrow, and move over southern Arkansas by early Friday," the hurricane center said.
Isaac, which was a tropical storm last week in the Atlantic Ocean, killed nearly two dozen people in Haiti and the Dominican Republic before starting its journey across the Gulf of Mexico.
On Tuesday, Isaac made landfall as a Category 1 hurricane.
CNN's Brian Todd, Soledad O'Brien, Ed Lavandera, Martin Savidge, John Zarrella, Steve Almasy, Joe Sterling, Anika Chin, Greg Botelho, Mike Ahlers, Aaron Cooper and Ed Payne contributed to this report.