http://comics.ign.com/articles/672/672586p1.html
How many of these do you comic book lovers know? Is it a good list? What would you add?
MIA:
CRISIS ON INFINITE EARTHS (Monthly series 1985)
The Anti-Monitor destroys the DC multiverse, the following DC characters die off for good (notably, Barry Allen's Flash, Wonder Woman and Supergirl).
Among the dead:
Angle Man
Anti-Monitor
Aquagirl
Bug-Eyed Bandit
Clayface II
Crime Syndicate of America (all members)
Dove of Hawk and Dove
Farmer Boy (of Sgt. Rock's Easy Company)
Barry Allen's Flash
Green Arrow of Earth-Two
Huntress of Earth-Two
Icicle
Immortal Man
Justice Alliance of Earth-D
Kid Psycho
Kole
Lex Luthor of Earth-Two
Lex Luthor of Earth-Three and wife Lois Lane-Luthor
Lori Lemaris
Lord Volt of Earth-Six
The Losers (Johnny Cloud, Gunner, Sarge, Captain Storm)
Maaldor the Dark Lord
Mirror Master I
Monitor
Nighthawk
Prince Ra-Man
Princess Fern of Earth-Six
Robin of Earth-Two
Shaggy Man II
Starman IV (Prince Gavyn)
Sunburst
Supergirl of Earth-One
Ten-Eyed Man
Wonder Woman of Earth-One
Not only was the first "Crisis" deadly, but it had lasting effects on the DC universe and is considered canon.
KINGDOM COME (1997) was another biggie, practically the entire "next generation" of superheroes and villains was wiped out in a collossal nuclear blast, I'm not sure if this is part of DC canon though.
IDENTITY CRISIS (2004) the murder of Elongated Man's wife while not only chilling, kicks off a lot of other issues including how the Justice League deals with villains who "learn too much" to creating new enemies and schisms within the League (both Atom and Firestorm hang up their capes).