But the incumbent senator didn't fight back until very late, or make any of these issues a focal point of her campaign, giving her opponents free rein on what they could say.
Perhaps another political shift that Murkowski didn't gamble on was the power of Palin's endorsement and the Tea Party's influence, one that many say helped change the course of the race.
Palin's approval rating in the state has declined since she stepped down in July 2009. In a poll conducted in April by the Dittman Research Corp., 46 percent of Alaskans had a favorable view of Palin, while 52 percent held an unfavorable view.
But among the core GOP base, the former Alaska governor remains a formidable force. The same poll found that 71 percent of registered Republicans had a favorable opinion of the former vice presidential candidate.
Unlike some of her "mama grizzlies," Palin remained behind the scenes in Miller's campaign. She didn't appear in any TV ads or at rallies for him, and only recorded one robocall toward the end.
But it was Palin, Republican insiders say, who helped pull the purse strings. Her political action committee gave $5,000 to Miller's campaign, and helped with getting the Tea Party Express to bankroll much of Miller's campaign.
It's unusual for national money to pour into Alaska for midterm elections, except for when an incumbent is running. But Palin changed that game.
"With her kind of name brand, it was easy for the Tea Party to say, 'Give me your money, this was Sarah Palin's candidate,'" said veteran Alaska reporter Shushannah Walshe, who co-authored "Sarah from Alaska" and is a contributor to the Daily Beast.
Republicans say Palin's quiet emergence in the Senate race is a testament to the long-standing feud between the two families. Palin was one of a handful of candidates Murkowski's father, Frank, had picked to replace him in the U.S. Senate when he became governor in 2002. In the end, however, he ended up choosing his daughter, Lisa, despite allegations of nepotism.
Palin beat Frank Murkowski in the 2006 gubernatorial race as his ratings tanked.
Sen. Murkowski herself didn't enjoy as much popularity as some may have thought, as evident by this primary, Moore said.
"It was always lurking underneath the surface. How she was appointed in the first place allowed a lot of people to let her go quite easily," he said. "Most people don't kick incumbents out when they're reasonably popular, but people found out in the end their loyalty to Lisa really fundamentally wasn't very strong."
The cold relationship between Murkowski and Palin is widely documented. Murkowski took a stab at Palin for stepping down as governor. On Tuesday, she again assailed the former veep candidate for being out "for her own self-interest" and not "Alaska's interest."
Palin, meanwhile, targeted the family dynasty in her robocall for Miller.
"She's waffled on the repeal of Obamacare, co-sponsored cap-and-trade and voted for TARP," Palin said of the Troubled Asset Relief Program. "Joe Miller has the right ideas for Alaska."
Murkowski's loss would be a huge blow to the Republican establishment. Not only was she backed by the national GOP, she was also part of the Republican leadership. She would be the second incumbent to lose, after GOP Sen. Bob Bennett of Utah, and the third incumbent senator to take a fall.