Democrats control the Senate by a 53-47 majority. Two years ago, Republicans seized control of the House of Representatives in the 2010 mid-term election and hold a 240 to 192 majority.
In Florida, two-term Democratic Senator Bill Nelson faced minor opposition in his primary, but was expected to be in for a tough re-election battle in November against the Republican primary winner, U.S. Representative Connie Mack.
Mack, the son of a former senator, easily won the Republican primary over three other candidates and could edge out the incumbent Nelson in a general election, according to a recent poll. But political analysts said Nelson has ample resources to attack Mack.
"Tonight's results really show that a lot of Republicans are voting for the candidate they think will have the best chance of beating the Democrat" and putting aside negative concerns about individual candidates, said University of South Florida political analyst Susan MacManus.
Because of population shifts over the past decade, Florida added two congressional seats, but the redrawn districts pitted two incumbent Republicans against each other. Republican John Mica, a 20-year veteran, easily beat Sandy Adams, a favorite of the conservative Tea Party movement, in a central Florida district.
The Cook Political Report considers seven of the 23 Democratic-controlled U.S. Senate seats to be toss-ups. Nelson's re-election chances were seen as particularly tough. Three of the 10 Republican-held seats up for election this year are toss-ups.
"It's a 50-50 ball game right now," said Cook Political Report analyst Jennifer Duffy. "When I look at the map, I find it improbable that any party would have 52 (Senate) seats, with 51 more probable."
A 50-50 tie in the Senate would give control of the chamber to the candidate who wins the presidency - Democratic President Barack Obama or his Republican challenger, former Massachusetts Governor Mitt Romney.
A wild card in the Senate will be if former Maine Governor Angus King, an independent, wins the seat of retiring Republican Olympia Snowe. King has said he will not declare which party he will side with until after the November vote.
Wisconsin and Connecticut voters set the stage to fill U.S. Senate seats being vacated by retiring Democrat Herb Kohl and Joseph Lieberman, an independent who caucuses with the Democrats.
Wisconsin Democrat Tammy Baldwin, a seven-term U.S. representative and avowed liberal, ran unopposed in her party's primary. Former four-term Wisconsin Governor Tommy Thompson beat businessman and political neophyte Eric Hovde and two other candidates for the Republican nomination.
Thompson may benefit in the general election from Romney's choice over the weekend of Wisconsin congressman Paul Ryan as his vice presidential running mate, analysts said.
However, Ryan is a polarizing figure in Washington, where he led his party's push to cut domestic spending, lower taxes and scale back the size of the federal government as chairman of the House of Representatives Budget Committee.
The Connecticut contest was won by favorite Linda McMahon, a professional wrestling executive. McMahon is seeking another chance after she lost a Senate race two years ago despite spending $50 million.
On the Democratic side, U.S. Representative Christopher Murphy was favored to win the primary and has already been targeted by McMahon's campaign ads.
In June, a Quinnipiac University poll found Murphy with a slight lead over McMahon if the two candidates face each other in the November general election.
Minnesota Senator Amy Klobuchar, a Democrat, was predicted to be heavily favored in November against the winner of the Republican contest. The party-endorsed candidate, Republican state representative Kurt Bills, was leading handily with more than half the vote counted.
(Additional reporting by Edith Honan in New York, David Bailey in Minneapolis and David Adams, Tom Brown and Barbara Liston in Florida.; Writing by Andrew Stern. Editing by Cynthia Johnston and Christopher Wilson)