(CNN) Justice Anthony Kennedy's retirement from the Supreme Court has put the Senate on the cusp of an all-out war over his replacement and thrust an unexpected and hotly contested issue into the spotlight less than five months away from the midterm elections.

Most Democrats and progressive groups are bracing for a generational battle, fearing that abortion rights, LGBT rights and the Affordable Care Act's coverage of those with pre-existing conditions will all be in jeopardy if President Donald Trump's eventual nominee is confirmed.

Republicans, meanwhile, see the Supreme Court fight as a way to energize voters the party had feared would drift toward Democrats or sit out the midterms, by reminding them of the benefits of voting the GOP into power.

With a 51-to-49 majority in the Senate and control of the White House, Republicans have the power to fill Kennedy's seat no matter what Democrats do to try to block Trump's nominee.

"We have to pick a great one. We have to pick one that's going to be there for 40 years, 45 years," Trump told supporters at a campaign rally Wednesday night in North Dakota.

But the battle could pose challenges to both parties in the near term, particularly Senate Democrats running for re-election in states Trump won in 2016. Those senators will have to decide between angering their party by voting for the President's nominee and giving Republicans a new opening to attack them ahead of the midterms by voting against Trump's choice.

Already, some of the most vulnerable senators were avoiding taking positions on what had quickly become a rallying cry for most of their Democratic colleagues: that the confirmation vote be scheduled after the midterm elections.

"There's a process we are going through. There's a decorum we should have. It's a shame when the place breaks down," said Democratic Sen. Joe Manchin, who is running for re-election in West Virginia, where Trump won by 42 points.

North Dakota Sen. Heidi Heitkamp, a red-state Democrat who has made working with Trump a cornerstone of her 2018 re-election campaign, distanced herself from some Democrats and suggested the President's nominee should get a vote before the midterm elections.

"I was taught that two wrongs don't make a right," Heitkamp said, a nod to the fact that Senate Majority Leader Mitch McConnell delayed voting on Merrick Garland, President Barack Obama's 2016 pick for the court, until after the presidential election.

Manchin and Heitkamp, along with Democratic Sen. Joe Donnelly of Indiana, were the only Democrats to vote for Trump's first Supreme Court nominee, Neil Gorsuch.

For Republicans, meanwhile, a high-profile battle over abortion rights and health care could alienate women in particular and complicate their chances at holding Senate seats in swing states like Nevada and Arizona, as well as in the suburban battlegrounds that will determine control of the House.

Rep. Jacky Rosen, the Democrat looking to unseat Republican Sen. Dean Heller in Nevada, a state that voted for Hillary Clinton in 2016, cast the fight as key to the "future of the Supreme Court" and knocked Heller as nothing more than a "rubber stamp" for Trump who could "jeopardize Roe v. Wade."

For his part, Heller tried to cast the issue as a coming fight against "obstructionist" Democrats.

"Think of it this way -- if there is another vacancy, who do you want picking the next Supreme Court Justice? President Trump and Senate Republicans or obstructionist Democrats," Heller said in a fundraising email sent shortly after Kennedy's retirement announcement.

As Democratic senators weighed the politics surrounding Kennedy's replacement, progressive activists and other arms of the Democratic Party prepared for a massive fight that could ripple through elections in 2018 and 2020.

Democratic National Committee Chairman Tom Perez said Kennedy's retirement should "remove all doubt" about the importance of November's midterms, while outsiders began to debate how Minority Leader Chuck Schumer, a new York Democrat who urged Republicans on Wednesday "to follow the rule they set in 2016" and "not to consider a Supreme Court justice in an election year," should direct his caucus.

One organizer at a major progressive activist organization warned that simply calling out the GOP for hypocrisy wouldn't be enough to mobilize a grass roots that's been worn out by almost two years of near-daily political battles.

"If we decide to make this a DC, think tank-first approach, that's where we're going to get our asses handed to us," the organizer said. "This fight can't be about (saying), 'This is not normal!' This is not normal!' -- that's not what this is. We need to lay out the stakes."

But even then, Democrats, with only 49 votes if they stick together, would have to either convince a couple of Republicans to flip or consider extreme measures -- potentially unprecedented acts of civil disobedience, one senior Democratic aide on the House side said -- to block the nominee. Recent history suggests that, as with the brief government shutdown over the Deferred Action for Childhood Arrivals program earlier this year, Senate Democrats might not have the stomach for that brand of politics.

Potential 2020 Democratic presidential candidates, including Sens. Kamala Harris of California and Elizabeth Warren of Massachusetts, called on Senate Majority Leader Mitch McConnell to wait until after the midterms to replace Kennedy.

"This Supreme Court vacancy puts issues that affect every single American in the balance, from a woman's constitutionally protected right to make her own health care decisions to privacy, equality and civil rights," Harris tweeted.

"I hope that my Republican colleagues who believe that women, not the government, have the right to control their bodies will stand with those of us who oppose any nominee who would deny women the right to choose," said independent Sen. Bernie Sanders of Vermont.

Adam Jentleson, a former Harry Reid aide, tweeted that the most important question is whether Democrats "have the will to fight against overturning Roe v. Wade in an election year where women are driving Dems' strength."

Jentleson tweeted that he doesn't know how red-state Democrats will vote, "but this is definitional."

"Any Democrat who votes for Trump's nominee (assuming it's someone from his list of 25) will be voting to overturn Roe v. Wade."

On the other side of the aisle, Republicans were gleeful at the prospect of moving from Kennedy -- a swing vote on the Supreme Court -- to a Neil Gorsuch-style conservative who would cement a five-vote majority for potentially decades to come.

"I think that's the one thing energizes conservatives more than anything else, is the Supreme Court," said Sen. John Cornyn of Texas.

A Republican involved in Senate races said Democrats will have to choose between a base that wants a big fight against Trump's nominee and moderate voters in their states. That Republican called Kennedy's retirement "a majority saver."

The Koch brothers' political network was also revving for battle. Sarah Field, the vice president of judicial strategy for Americans for Prosperity, told CNN the group will spend "seven figures on the fight."

"We've essentially been spending the last six months preparing for this moment, working with activists and connecting them with what's at stake," Field said.

Still, the fight could hurt Republicans in states with more Democratic or moderate electorates, like Nevada and Arizona. It could also prove damaging in House races, particularly in suburban districts, including 23 currently held by Republicans where Clinton won in 2016.

The Trump administration's efforts to undercut Obamacare's health care protections for those with pre-existing conditions are the subject of a legal battle, and a Democrat working on House races said the Supreme Court fight makes it easier for Democratic candidates to connect the courts to health care.