The two are locked in a tight race in the swing state that could determine which party controls the Senate next year.
Both the Ryan budget and the Obama health law would reduce future Medicare spending by about $700 billion.
Berkley told Heller it "takes a lot of brass" to attack her on the $700 billion in cuts when he'd also voted for them.
"I did not cut money out of Medicare guaranteed benefits," she said, arguing that vote extended Medicare's solvency by nearly a decade and its spending decreases mostly came from cutting reimbursement rates to insurance companies, not to direct care for patients.
The two also sparred over Berkley's ethics issues.
She's facing an investigation from the House Ethics Committee over whether she had a conflict of interest in supporting kidney dialysis programs in the state and opposing cuts to Medicare reimbursement for dialysis because her husband is a kidney doctor.
"My one and only concern was to protect the health and well-being of the people of the state of Nevada," Berkley said when asked about the controversy by a debate moderator.
"Character matters," Heller said. "It matters in life and it matters in the U.S .Senate. My opponent has a big problem. Do you know how unusual it is for the Ethics Committee to move forward on an investigation like this? It's big. It's huge. And she can't get away from it."
The two also fought over immigration — Berkley attacked Heller for supporting Arizona's tough anti-immigration law and opposing the DREAM Act, while Heller accused her of supporting "blanket amnesty."
Heller has led Berkley in most public polls, and held a six-point lead in a NBC/Wall Street Journal/Marist poll released on Thursday. But other recent public polls have shown a tighter, and tightening race — a poll from the conservative Rasmussen Reports released last week had Heller up by just one point.