The amendment to allow research using embryonic stem cells, which inspired a prominent Michael J. Fox television ad in support, became a lightning rod of national importance when commentator Rush Limbaugh attacked Fox's sincerity. The push to pass the referendum was a key factor in Missouri's crucial Senate race; Democratic challenger Claire McCaskill rode her support of the measure to take the seat of incumbent Republican Jim Talent, who opposed the measure.
Another controversial referendum, South Dakota' toughest-in-the-nation law that would have banned virtually all abortions, even in cases of rape and incest, was strongly defeated by voters.
That result was a tremendous blow to conservatives, as was Arizona, which became the first state to defeat a gay marriage ban.
Conservatives did prevail in seven states where voters approved constitutional amendments to ban gay marriage, though CBS News political analyst Sam Best notes that they didn't pass with as great of a margin as such bans did in 2004.
"We're getting closer to 50-50," he says. "It seems to suggest that people are warming to the idea."
Nationwide, a total of 205 measures were on the ballots in 37 states, but none had riveted political activists across the country like the South Dakota abortion measure. Passed overwhelmingly by the legislature earlier this year, it would have allowed abortion only to save a pregnant woman's life.
Lawmakers had hoped the ban would be challenged in court, provoking litigation that might eventually lead to a U.S. Supreme Court reversal of the 1973 Roe v. Wade decision legalizing abortion.
"This is a wake-up call to lawmakers in other states that America's pro-choice majority will not allow an assault on Roe v. Wade to go unanswered," said Nancy Keenan, president of NARAL Pro-Choice America.
Conservatives fared better with bans on gay-marriage, which won in seven states: Idaho, South Carolina, Tennessee, Colorado, South Dakota, Virginia and Wisconsin. Results were pending in Arizona, where it was trailing. Similar amendments have passed previously in all 20 states to consider them.
Colorado voters had an extra option: a measure that would grant domestic-partnership rights to same-sex couples. That was rejected.
Conservatives had hoped the same-sex marriage bans and other initiatives aimed at hot-button social issues like immigration might increase turnout for Republicans. Arizona passed four measures targeting illegal immigrants, including one making English the state's official language.
"In a lot of states across the country, the economy was an important factor," says Best. "The Bush administration is touting good economic conditions but voters don't seem to be seeing that."
In fact, Democrats — who looked for a boost of their own among low-income voters by pushing measures to raise the state minimum wage — won those wage hikes in all six states: Arizona, Colorado, Missouri, Montana, Ohio and Nevada.
Voters rejected a boost in the cigarette tax in California, where big tobacco companies spent more than $56 million fighting the increase that would have raised the average price of a pack of cigarettes to $6.55.
Missouri also rejected a cigarette tax hike. But in Arizona, where the measure was targeted to fund pre-school programs, the cigarette tax hike passed. South Dakota also approved a sharp increase in tobacco taxes.
In Ohio, anti-smoking activists won a showdown with R.J. Reynolds Tobacco. Voters approved a tough ban on smoking in public places and rejected a rival, Reynolds-backed measure that would have exempted bars, bowling alleys and racetracks.
The costliest ballot campaign — a state record of $133 million — was raised in the fight over California's Proposition 87. The proposal to tax companies drilling for oil in the state $4 billion to promote alternative fuels and energy-efficient vehicles was defeated.
Nevada and Colorado both rejected measures that would have legalized possession of up to an ounce of marijuana by anyone 21 and older.
Rhode Island voters rejected a constitutional amendment that would have allowed the Narragansett Indian Tribe and a Las Vegas-based gambling firm to build a casino in West Warwick. The vote marked the third major defeat on the gambling issue for the tribe and its corporate partner, Harrah's Entertainment.
Rhode Islanders supported a measure that would restore voting rights to felons on probation and parole.
Michigan voters decided to bar the state government from using race and gender to determine who gets into college, who gets hired and who receives contracts.
Elsewhere, land use was a hot issue, part of a backlash against a 2005 Supreme Court ruling allowing the city of New London, Conn., to buy up homes to make way for a private commercial development.
Eleven states considered eminent-domain measures barring the government from taking private property for a private use; Florida, Georgia, Michigan, New Hampshire, North Dakota and South Carolina approved them overwhelmingly.
Arizona approved a bill that would require governments to pay landowners when land use laws reduce their property value, but Idaho, Washington and California rejected similar measures.
Washington voters also rejected an attempt to repeal a recently-enacted tax on estates larger than $2 million.
South Dakota voters defeated a measure that would have made their state the first to strip immunity from judges, exposing them to the possibility of lawsuits. In Maine, Nebraska and Oregon, voters defeated measures that would cap increases in state spending.
In Arizona, voters were deciding on the most ballot measures — 19 — including four that stemmed from frustration over the influx of illegal immigrants. Four measures — expanding the list of government benefits denied to illegal immigrants, limiting lawsuit damages an illegal immigrant can win, denying them bail and making English the state's official language – all passed.
Voters weren't keen about another, more quirky Arizona measure: They defeated a proposal that would have awarded $1 million to a randomly selected voter in each general election.
By an overwhelming margin, Pennsylvania voters gave the state the go-ahead to borrow $20 million so that nearly 33,000 Pennsylvania veterans who participated in the Persian Gulf War can collect one-time payments of up to $525.