1st Amendment: -10 in foreign relations with Russia (Stalin only), Germany (Hitler only), Italy (Mussolini only), and all civs under Police State or Theocracy (With restrictions on religion).
2nd Amendment: -10 in foreign relations with those with gun control. 2/3 of citizens are

"Guns are killing our citizens!"
Prohibition: All citizens mad. "Hic... You better let us drink the booze!", +

for all other nations for smuggling alcohol to the country with Prohibition.
US Elections 2008: All citizens in civil disorder. "So many candidates, but I need one who has all the qualities of all Democratic/Republican candidates!"
Science: All citizens with religion are

. -2 with all religious civs, and civs with religion. "God created everything, not BIOLOGY!"
Religion: All scientists quit. -2 with all Scientific Civs. "Biology was how nature came!"
Biologist Priest: Both effects of Religion and Science. -4 with all religious civs, scientific civs, and allreligious cities. "Are you with us or not, you oxymoron?"
Classical Music: All people born in modern age cities are

. "This music sucks ass!"
Rock 'N Roll, Punk, Rock, etc.: All people born before Modern Age are

"This music is too loud, vulgar, scandalous, etc."
Concerto with 50 Cent: Effects of the two above. "You insane? That music is crap!" -20 in foreign relations. "ARGHHHH! My EARS!"
Leaning Tower of Pisa: Unless you invest 20 gold each 5 turns after its built, it will fall and crush all citizens/buildings within radius.
Venice: City will flood due to global warming. -100 to all civs with environmentalism to all civs with polluting industries. "You caused an uber cultural city to sink!"
Polar Ice Caps: Once Global Warming starts, these melt and cause oceans to rise. About 1/4 - 1/2 of all land is lost, as well as anything on it.