But Connecticut's attorney general, Richard Blumenthal, kept his state's open Senate seat in Democratic hands, fending off pro wrestling entrepreneur Linda McMahon.
Paul, who beat Democratic Kentucky Attorney General Jack Conway, is an ophthalmologist who had not sought office before. His father is Rep.Ron Paul of Texas, a hero to many libertarians. GOP Sen. Jim Bunning is retiring from the seat.
Rubio, a former Florida House speaker, is not a political newcomer. But he defied his party's establishment nonetheless, refusing to stand aside for Gov. Charlie Crist in the Senate race. Crist ran an independent effort, but Rubio comfortably defeated him and Democratic Rep. Kendrick Meek. The Florida seat's previous two occupants were Republicans who stepped down.
Christine O'Donnell, another tea party darling, lost to Democrat Chris Coons in Delaware. She also had won a stunning GOP primary victory, beating longtime Rep. Mike Castle, who was expected to top Coons. But she raised eyebrows with curious comments about witchcraft, the First Amendment and other topics, and failed to extend her popularity to the broader November electorate.
Tea partiers were hoping for up to three more Senate victories in western states. They included Nevada, where Sharron Angle hoped to beat Senate Majority Leader Harry Reid, and Colorado, where Ken Buck took on Democratic Sen. Michael Bennet.
But a tempestuous three-way race in Alaska threatened to let Democrat Scott McAdams win a once-hopeless race for GOP Sen. Lisa Murkowski's seat. Murkowski was running a rare write-in campaign after losing the Republican primary to another tea partier, Joe Miller.
In New Hampshire, Republican Kelly Ayotte kept her party in control of the seat being vacated by Judd Gregg. The former state attorney general defeated Democratic Rep. Paul Hodes.
Rob Portman won the Ohio Senate race, keeping a Republican in the seat that Sen. George Voinovich is vacating. Portman spent 12 years in the U.S. House starting in 1993. He later was budget director and then U.S. trade representative under President George W. Bush. Portman defeated Democratic Lt. Gov. Lee Fisher.
And Rep. Roy Blunt kept Missouri's open Senate seat in Republican hands.
Easily winning re-election as expected were Sens. Mike Crapo, R-Idaho, David Vitter, R-La., Charles Grassley, R-Iowa, John McCain, R-Ariz., Jim DeMint, R-S.C., Richard Shelby, R-Ala., Tom Coburn, R-Okla., Richard Burr, R-N.C., John Thune, R-S.D., Johnny Isakson, R-Ga.,Ron Wyden, D-Ore., Patrick Leahy, D-Vt., Kirsten Gillibrand, D-N.Y., Charles Schumer, D-N.Y., and Barbara Mikulski, D-Md.