Buy controlling interests in the Washington Post, the New York Times, and at least one major TV network (e.g. CBS has a $17B market cap). Destroy reputations as desired. 
I’d further my goals and causes, but beyond that nothing spiteful. Holding a grudge is letting someone or something occupy your mind rent free. Plus it’s just bad Karma for you.
I would feel very anxious in not being able to place all that money to good use right away, but hopefully I would have enough time to establish an ongoing trust that would be able to further my causes eventually.
In my opinion, spite is for losers.
I’d give it to the school where I got my master’s degree, on condition that they make my former advisor do something humiliating in public (to be posted on YouTube, of course), then fire him. He wouldn’t know about the firing condition before it happened, so he’d think he’d need to do the humiliating thing to keep his job.
This is fantastic. Bravo.
Spite, Part Two: I’d endow a chair at UC Berkeley for $100 million, but only if they name it for and fill it with conservative economists. I’d wave the same amount in front of TCU for a Chair of Demonology. Notre Dame gets a Martin Luther Chair offered. Then I’d buy and subsequently demolish every iconic skyline feature of every city east of Denver, just to screw with all of their tourist gee-gaws.
They’re just vile. Among the multitude of crap they’ve pulled on their neighbors:
Called the cops repeatedly on the couple down the street who had a low key, small (no loud music/noise) wedding reception in their back yard on a sunday afternoon. Their main bones of contention were that the metallic balloons were too bright and exacerbated the wife’s migraines and that people parked on the street (legally).
Reported another woman to CPS who had just had a baby because (being summer) she had her windows open sometimes and the crying meant that she was abusing it. We actually live closer and it was ‘normal’ baby noise. Oh, and she was diagnosed and treated for breast cancer during the pregnancy & infancy which they knew.
Had their lawyer threaten to sue the 14 year old who accidentally sprayed water through the fence into their yard and on them (doubtful).
Woman lost her purse, kind samaritan tried to drop it off at her house but since no one was home they came out (they have to know everything that goes on with everyone) and offered to give it to her. Then they informed her husband that she had condoms in it (searched the purse) and that this was a sign of having an affair (no- they just use condoms).
Tried to stop the police approved yearly block party because it infringed on their rights to have people partying on a street (not sure how).
Have informed anyone with children that they aren’t “allowed” to have friends over and play outside because it bothers them.
Screamed, “we know you’re dealing drugs” & “we see your drugs” at the great teens next door when they were carrying bags full of drama club props into their house. (This was a black family - they’ve been heard to make comments about persons of color propensity for criminal behavior)
I could go on & on. They’re just jerks. We ignore them except for my husband flipping the bird when he sees them outside. They’ve managed to intimidate some of our neighbors into stepping very softly just because they don’t want to deal with the aggravation.
If I had tons of money I’d slowly buy up every house on the block. Then I’d rent them out at miniscule amounts to anyone I think could annoy them. Large multi generational immigrant families. Someone who has a garage sale every weekend. Anything to be nastily spiteful.
Once when flying out of Lindbergh Field, I started speculating how much it would cost to buy up every home and business on the Point Loma peninsula and turn it into a nature preserve. I figure 50 billion would do it. Where’s the spiteful part? I started imagining how it could be done without inflating home prices. I figured that if I bought all the homes currently for sale, then rented them out to a bunch of stoners at below market rates, I could keep property values low. After ten years or so, Point Loma would be de-gentrified into a bunch of pothead renters. Then would come the eviction notices followed by bulldozers.
Buy the New York Yankees. Fire them all - players, coaches, management. Put a bunch of minor leaguers out there to play - pay them league minimum.
Buy van Gogh’s works and destroy them.
You actually think it would be possible to shock Notre Dame’s theology department? Guess again! There are ALREADY numerous Protestants, atheists, Jews, and ____ (fill in your preferred religious minority) on the Notre Dame faculty.
Indeed, orthodox Roman Catholic believers are probably a MINORITY at most Catholic college theology departments.
I’ll admit it, I’m an asshole. I wouldn’t be spiteful, I’d be heartless.
If I had that kind of money, I’d go and buy every low-income apartment complex within 15 miles of my home, raise rents, and either demolish them and replace them with parkland or refurbish them such that they wouldn’t be wretched hives of scum and villainy. Of course, I’d bribe or ruin anyone who tried to get in my way as well.
If I had to be spiteful, I’d probably donate a huge sum of money to the University of Texas for some new land for a new school of some kind, but I’d stipulate that the outside of the building would have to be maroon and white in perpetuity (no repainting a different color), and that it would be named after my Dad and Uncle, who are two of the hugest, most rabid Aggies I’ve ever met.
That does it. I’m writing you out of my will
SS
This doesn’t just win the thread. It wins the entire internet.
Give a few million to my mother in law (whom I actually really like, and who couldn’t morally live with herself if I gave her more than that). Watch the money obsessed bastard from hell who donated the DNA for my spouse go crazy trying to get it. He’d probably sue to try and get part of it, never mind that the divorce was official five years ago and all their kids are legal adults now. I’d hire better lawyers for her, and watch the fun.
Heh. I’m sure my ex-wife would sue for money too, even though the divorce was completed 7.5 years ago and we were only married (including the divorce time) for 1.5 years. AND she settled out of court recognizing that she owned me money.
The house two doors down is for sale. If she tried to sue for money, I’d buy it and move in for a little while.
Watch out, I am sending my army of professional bad neighbors your way 
Realistically speaking, I wouldn’t. If i were somehow gifted with an insane amount of money I’d probably be bending over backwards to be super-duper good and moral.
But what kind of fun is that?
1.) The ex who most completely broke my heart is in love with Disney World and wanted to honeymoon there if we ever got married. Buy Disney World. Life-time ban.
2.) My undergraduate college was so cold most of the year that we could have raised penguins. Build an exact replicate of it 500+ miles south of its current location. That includes landscaping the location to match every hill. Offer the entire faculty twice their present salaries to relocate.
3.) The pro-life movement is proud to have made it prohibitively difficult to maintain abortion services in certain communities. Paging Planned Parenthood…you’re about to open a lot of new clinics. Spiteful because the building program would follow a “twice as big as the old one and with a neon sign” approach.
Take 40 billion of it and burn it publicly while giggling like a school girl.
Did you post this to spite the people who post in this thread? 
I’d hand over the cash to the UN, providing they recognize Palestine. Regardless whether they accept it or not, I’d piss off some might powerful people.
Oh, and I’d buy Phred Phelps and/or Jack Chick his own TV station.
TCU would reply:
Thank you, brother in Christ! we certainly do need to study demons and their pernicious influence in our society. We will gladly use your money to counter the homosexual movement, the so called “pro-choice” movement and other demonic incursions. God bless you! (and we heard about your donation to Berekley. God Bless you for that too.)