Addressing the U.S. Conference of Mayors in Washington, Biden -- who led the White House task force that developed the Obama administration's proposals for addressing gun violence -- said the nation has "an obligation to respond intelligently" to the deaths of 20 students and six adult staffers at Sandy Hook Elementary School.
"Newtown ... affected the public psyche in a way I've never seen before," Biden said.
He said gun violence has become routine in U.S. society to the extent that it is "defining deviancy down," The Hill reported.
"We can't wait any longer to take action," Biden said. "The time has come."
Philadelphia Mayor Michael Nutter, president of the U.S. Conference of Mayors, told the gathering in Washington Thursday the Sandy Hook massacre is having an effect on the debate unlike that following other massacres, including those at Columbine and Aurora, Colo., Virginia Tech and Tucson.
"A tragedy in Newtown that even after all the others we still cannot imagine ... a terrible unforgivable moment in American history," Nutter said. "We cannot get those lives back ... we can and we must act to help protect the lives of those in the future.
"This has nothing to do with taking guns away from those who lawfully own them," he said. "We respect the Second Amendment ... but the right to own a firearm should not interfere with my right to live."
U.S. Sen. Rand Paul, R-Ky., said he will try to kill parts of President Barack Obama's executive actions to curb gun violence, suggesting the president has a "king complex."
Rand said on Fox News Wednesday he will seek to nullify any of Obama's executive actions announced Wednesday "that smacks of legislation."
"I'm very concerned about this president," Paul said of Obama before discussing executive actions taken by President Franklin D. Roosevelt during his tenure in the White House.
Roosevelt served three full terms and died in office during his fourth.
"FDR had a little bit of this 'king complex' also," Paul said. "We had to limit FDR finally because he served so many terms that I think he would have ruled in perpetuity, and I'm very concerned about this president garnering so much power and arrogance that he thinks he can do whatever he wants."
A summary provided by Paul's office said his initiatives would try to nullify any executive actions that could be construed as breaching the Second Amendment, Roll Call reported. Paul said he wants to ensure he or others have legal standing to challenge the executive actions in the federal court system.
Paul's efforts would try to block funding to implement executive orders on gun control or related to restrictions on the Second Amendment, Roll Call said.
Paul said he thought his proposals concerning executive action had little chance of moving in the Senate, but he believes he has more opportunity to block gun-control legislation from advancing in the Senate.
"I think there are a few Democrats that will worry about going home to West Virginia or other states like that and voting for a ban on guns," he said.
Among the things Obama called for Wednesday was congressional action on several gun-control measures, including restrictions on high-capacity ammunition magazines and an assault weapons ban.
National Rifle Association President David Keene told ABC News: "All bets are off when a president really wants to go to war with you. We're gonna be there and we're gonna fight it."
Most of Obama's 23 executive actions, which don't require congressional approval, sought to fill holes in law enforcement, mental health and school safety -- allowing federal research into gun violence, pressing agencies to submit more mental health records into the existing background-check system and providing funding for schools to hire law enforcement officers.
Obama vowed to rally the nation on the gun violence issue.
"I will put everything I've got into this, and so will Joe," he declared, standing next to Vice President Joe Biden in a White House room filled with gun-control advocates and family members of shooting victims.
Keene, whose lobbying organization is the nation's largest gun-rights advocacy group, said NRA members would hold accountable any politicians who "sell them out to some pie-in-the-sky scheme such as the president is proposing."
At the White House ceremony, which included four children who had written to the president asking for stronger gun laws, Obama encouraged Americans to ask their members of Congress, "What's more important -- doing whatever it takes to get an 'A' grade from the gun lobby that funds their campaigns, or giving parents some peace of mind when they drop their child off for first grade?"
Keene told ABC the NRA remembers the 1994 federal assault-weapons ban passed Congress, despite initial lawmaker opposition, in part because of pressure from President Bill Clinton.
Obama noted former Republican President Ronald Reagan, "one of the staunchest defenders of the Second Amendment," also wrote to Congress in 1994 to urge support for the assault-weapons ban.
Congress passed the 10-year ban Sept. 13, 1994, and Clinton signed it into law the same day. The ban expired 10 years later, as part of the law's "sunset provision."