A lot has happened since I joined in 2000. The highlights:
I got married.
We had a son, who is now five years old.
I got laid off twice, and found new jobs, twice.
I bought a house.
Oh, good lord, I don’t know if I can pick a biggest. I lurked way back on AOL which was probably when I was in high school! I don’t know which to pick among: graduated from college and grad school, got married, had a kid, and now my father died.
Since 2003? Same wife, same house, same job, same car. Nobody close to me has died. I’ve got two more grandchildren and I started riding a motorcycle about five years ago. That’s about it!
Since the thread title asks for ONE event, I’m going to go with “went to work for the USPS, immediately more than doubling my annual income.”
Joined in 2000 at age 14. I can hardly remember anything significant in my life that hasn’t happened since I joined the Dope:
Started and finished high school, college, and two masters degrees. Moved across the country twice and to another country briefly. Mom survived breast cancer. Next week moving halfway back across the country with my fiancé and our dog.
Joined in 2000.
My mother died at 92.
Decided not to move back to NYC.
Both cats died (16 and 20). Adopted 2 more.
Continue to lose friends to AIDS.
Traveled to Europe 11 times, hiked throught the Southwest.
Had heart surgery: new aortic valve (bovine), quadruple bypass.
My art career has shifted to new medium (complex photo montages)
Celebrated 27 years with partner; still not allowed to marry.
Currently suffering effects of diabetes, dreading turning 70 this year.
Bought a cello. Will begin to learn to play it on my 70th birthday.
Since 1999? Wow. . .
Married (though we were living together when we both started posting here)
Graduated College
Moved to Texas
First Teaching Job
Bought a house
Lost 120 lbs
Had a son
Changed jobs
Stop following the rules, you’re making us look bad. 
Lived in multiple homes in multiple places, had multiple jobs, and multiple pets. Have gone from a devout, church-going Evangelical to an agnostic. Have gone from a Rush Limbaugh conservative to a rock-ribbed libertarian*. Have taken up smoking pot.
*In retrospect, I’ve always been a libertarian, I just didn’t know it until I started studying what the term means.
Got laid off in Dallas in 2005
6 month contract in Redmond, WA in 2006
6 month contract in Tulsa, OK in 2007
12 month contract in Redmond, WA in 2008/9
3 month contract in Indianapolis, IN in 2009
6 week contract in Hot Springs, AR in 2009
9 month contract in Irving, TX in 2009/10
9 month contract in Bloomington, MN 2010/11
4 month contract in Englewood, CO in 2012/13
6 month contract in Norcross, GA in 2013
Mother died in February 2013
Mother-in-law died in May 2013
4 month contract in Boise, ID in 2013/4
8 month contract (so far) in Wilmington, OH in 2014/5
More pets than I care to think about, either vanished or euthanized
Fun times!
Got my Ph.D., then got engaged to oft wears hats. Had to do the first before the second, so he could call me Dr. Girlfriend for a while 
Developed back issues (which will probably cause problems for the rest of my life now) lost my job, couldn’t really return to what I was doing with a bad back, went through nearly 2 years unemployment, then a series of low level jobs while trying to work out what to do with my life.
Haven’t succeeded in working out anything approaching a long-term plan yet.
Lost my remaining grandparents, moved house, got axolotls, trained as a beekeeper (waiting on site approval to actually get bees though).
Same house, same job, same wife. Got some grandkids. Shaved off mustache, it scared everybody, grew it back. Lost both parents, inherited a tidy sum. Quit smoking/gained weight.
Both kids finished their education and accumulated 7 degrees between them.
Both kids got married.
No more tuition payments. No more payments to the barn for the horse.
As for me, same house, same job, same wife. When I retire in a year things will change more.
Fathered 2 kids, 7 years apart
Had a vasectomy. 
I have lived in 6 different countries since I joined here.
I have a daily one-stop online shop for viewing random tidbits of fact and heresay. Before SD, I visited several different single-topic forums.
I left my job after 26 years in real estate.
I broke off my wristbone, leading to a permanently disabled hand.
I got a job as a cashier in a discount store. Much less stress.
Joined in 2003.
Four siblings and MIL have died since then. Newfoundland #1 and Terrier have also died. Newfoundland #2 came to live with us.
Kids grew up. Daughter married and moved away. Son in college still at home.
Same job, same house, same spouse. Like the job well enough but not so thrilled about the house. Feel lucky that spouse and I are still happy to be together at the end of the day.
Joined in 2011, since then:
2nd niece born September 2011
Changed jobs December 2011
Changed jobs December 2012
Went back to school February 2013
New job #3 April 2013
Grandmother died November 2013
Broke up with long-time boyfriend June 2014
I’ll graduate from school next month, still living in the same place and driving the same car.