(CNN) Millions of travelers are stressing out as powerful storms rolling over the East Coast interrupt or delay their return home from the Thanksgiving holiday weekend.

The weather has already caused a plane to slip off a runway while it was landing at Buffalo Niagara International Airport Sunday, Niagara Frontier Transportation Authority spokeswoman Helen Tederous told CNN via email.

It also led to a 25-vehicle pile up on Interstate 68 in Garrett County, Maryland, about 20 miles from the state's border with West Virginia. State police said heavy fog created limited visibility in the area and the National Weather Service said there was winter storm advisory for that area.

A day earlier in Chamberlain, South Dakota, nine people were killed when a plane crashed during blizzard-like conditions.

Airlines have delayed flights across the country on what is expected to be the busiest travel day in the US . American, Delta and other airlines issued travel waivers for those who want to cancel or change their plans.

On Sunday evening, nearly 6,500 flights were delayed within, into or out of the United States and more than 800 had been canceled, according to FlightAware.com. Travel impacts are expected to last through Monday, the weather service said.

About 50 million in the US are under some kind of winter weather alert.

The winter storm terrorizing the Northeast now already pounded the Upper Midwest with heavy snow, the National Weather Service said. Meanwhile, the West Coast is dealing with snow, floods and power outages.

Blizzard-like conditions will finish off the holiday weekend in the Great Lakes region, the weather service said, while up to 12 inches of snow may cover parts of the country spanning from the Dakotas to Michigan, it said

Many roads in Duluth, Minnesota, seen here Saturday, are "extremely treacherous," the National Weather Service says.

By Tuesday, parts of the Northeast will see up to a foot of snow, the service said. New York will see up to 2 inches of snowfall an hour Sunday and Monday, it said , making for dangerous roads as the snow piles up. Downed trees and power lines are also possible.

Heavy rain will hit New York City on Sunday evening before transitioning to a snowy mix by morning, and the city can expect 3 to 5 inches of snow by Monday's end, forecasters say. Gov. Andrew Cuomo has placed the National Guard on standby, he said.

Rain will stretch from coastal areas in the Northeast to farther south where it will be accompanied by thunderstorms and strong wind gusts, the weather service said.

"A cold front will be positioned from central Ohio, arcing eastward near the Appalachians, then south-southwestward into the Florida Panhandle," it said. Thunderstorms are possible along that front, but the system should be out of the Southeast by Sunday night, according to CNN meteorologist Madeline Scheinost.

In Massachusetts, the state Emergency Management Agency issued an "awareness statement" warning of 8 to 12 inches of white stuff over much of the state's interior and up to 17 inches on the eastern slopes of the Berkshires. Wind gusts could reach up to 45 mph along the coast, with Cape Ann and outer Cape Cod suffering the worst of the bluster.

Rain and wind in California

A West Coast storm is expected to hammer everything from Seattle to south of Los Angeles, bringing feet of snow to areas that sit at 6,000 feet or higher. Forecasters advise chains will be necessary to navigate roads in mountainous regions -- though white-out conditions in some areas may make driving especially dangerous.

"Travel is HIGHLY DISCOURAGED after 10 a.m. for the Coastal Range/Shasta County," the weather service's Sacramento office warned.

Shasta County is located between Sacramento and the Oregon border.

"Some flooding is possible in parts of Northern California, especially for areas with burn scars," the weather service said . "Meanwhile, the Sierra Nevada could see snow measured in feet."

In parts of Southern California, about 9,600 customers were in the dark, Southern California Edison said. The utility said the outage was storm related, after winds and snow-covered trees downed wires.

"No Wi-Fi, no electricity, so it's like we're back in the 1800s," Fabrice Vignati who was in Crestline --- about 70 miles east of Los Angeles -- told CNN affiliate KTLA.

The utility said it would be passing out firewood to affected residents with the help of authorities.

The storm will linger over the state through Tuesday, the weather service said

Impacts on busy travel day

Sunday, expected to be a historically busy day for US airlines , will see an anticipated 3.1 million passengers, according to Airlines for America, an airline trade organization. A record 31.6 million passengers were forecast to travel on US airlines during the Thanksgiving holiday period, up 3.7% from last year.

Due to delays and cancellations, Delta Airlines announced weather waivers for nearly two dozen cities in the Northeast for Sunday and Monday, including airports in Boston and the New York area.

American Airlines issued waivers for passengers traveling Sunday and Monday on flights to and from New York's John F. Kennedy and LaGuardia airports as well as Newark and the airline's hub in Philadelphia. Other cities in the American Airlines announcement include Boston, Buffalo, Pittsburgh and Toronto, Canada.