(Image Credit: Eric Gay/AP Photo)

A reference to John F. Kennedy has become the highlight of a vice presidential debate for the second time in history and Twitter was all over it.

Vice President Joe Biden and Rep. Paul Ryan disagreed Thursday night on some numbers crunching. Ryan was in the process of defending his plan to cut taxes and mentioned Kennedy as an example of someone who had made cuts in tax rates work.

"Jack Kennedy lowered tax rates, increased growth," Ryan said at the Danville, Ky. debate.

"Oh, now you are Jack Kennedy?" Biden asked sarcastically.

Twitter responded with 58,275 tweets per minute after Biden's Kennedy reference, which was a high point for the debate.

In the 1988 vice presidential debate, the Democratic nominee, Lloyd Bentsen, famously told Dan Quayle he was "no Jack Kennedy."

"Senator, I served with Jack Kennedy, I knew Jack Kennedy, Jack Kennedy was a friend of mine. Senator, you're no Jack Kennedy," Bentsen said.

The crowd in attendance that night shouted and applauded Bentsen's remark, but there was no crowd reaction Thursday night after Biden's Kennedy reference.

The other top moment that generated buzz on Twitter was when Ryan slammed President Obama's signature health care law, saying, "They got caught with their hand in the cookie jar turning Medicare into a piggy bank for Obamacare."

The "cookie jar" comment cam in second place with 55,540 tweets per minute.

ABC News' Martha Raddatz was also a hit on Twitter as she moderated the debate. Her Twitter followers increased from 6,000 to more than 20,000 during the 90-minute debate.

While there was no Big Bird moment this time around, Biden's constant laughter took over much of Twitter with more than 500,000 mentions.

Even celebrities had fun with the debate on Twitter. Actor and comedian Patton Oswalt had one of the most retweeted items of the night when he said, "Ryan is a nervous Walmart manager. Biden is an irate customer with the receipt, the warranty & he's friends w/ the store owner. #debate."

The former "King of Queens" actor's joke was retweeted more than 8,000 times and one of the top tweets of the night, according to social media tracking site Topsy.com.

Top-rising searches on Google during the debate were "Biden," "conflating," "malarkey," "who is winning the debate" and "how old is Paul Ryan."

"With all due respect, that's a bunch of malarkey," the vice president said after a Ryan attack on the administration's foreign policy.

"Malarkey," slang for "nonsense," was mentioned more than 20,000 times a minute, Topsy.com reported.