This might be a YMMV, but when the light from the radiation began to fade, the first thing you see is some man-shaped figure. I thought it was the Lone Wanderer's father. It was completely self inflicting, but I thought the Wanderer mistaking Jefferson as James was a CMOH.
The entirety of James's efforts with Project Purity. He leaves Vault 101 to pursue it, leaving behind a perfectly happy and safe life with his friends and child, he could have lived out his life in contentment, but he couldn't forget about the project. He braves the Wasteland to find the one man who may know how to finally get it working. To keep it out of dangerous hands, he sacrifices his own life. And the technology he uses to get it working could be used to terraform a small section of earth into fertile, living soil again, we know this based on the first two games, but he plans to use it for the project. He gives up the change to use the GECK to terraform a small piece of paradise so he can bring clean water, and hope, to everyone in the wasteland. And why? Because it was his wife's dream, and because there are so many people out there suffering, and he can do something to make their lives easier. James wants to improve the lives of everyone he can, and he will do anything to succeed including giving his life. Your PC may be The Messiah, but it obviously runs in the blood.
Doctor Li: So many years have passed. Is it really still worth trying? James: How could it not be worth improving the lives of everyone in the wasteland? What could be a more worthy cause? Doctor Li: You haven't lost any of your passion, have you James.
Convincing the Overseer to open the vault in the "Trouble on the Homefront" quest. This exchange says it best:
Overseer: We're the last bastion of pure humanity, and we're doomed.
Lone Wanderer: Humanity isn't about genetics. It's about never giving up hope, even now.
Anyone can finish Moira's survival guide by half-assing and bull-shitting their way to its completion, but doing it right? It goes on to to become one of the most helpful resources in the entire wasteland. In Fallout: New Vegas it has spread all the way to the Mojave and even helps the Courier buff up his/her survival skill.
Even better, the best version of the Guide has Moira actually credit you as the lead author, not just research assistant.
If you BS your way to the end, you can meet barely-equipped travelers who mock your work. If you do okay on it, you run into travelers who have some gear and survive. Go the extra mile and complete all of the requirements? Well-armed, well-armored travelers who easily cut down their enemies and thank you profusely for what you did.
Also, Moira is just so happy that it worked out well. It's more personally rewarding than the end of the main plot.
You can encounter the body of a murdered wastelander, who has a letter addressed to his brother. He apologizes for stealing his brother's most valuable goods, and gives directions to find his treasure. In the hiding place, all the treasure is is a couple of old comic books. Virtually worthless, but not to them.
Three Dog frequently updates his listeners on the actions of the player character, with a particular spin placed on his / her exploits depending on whether you have good, neutral or bad karma. If you reach Level 20 with good or very good karma, this is what Three Dog will say about you — and it will warm your heart to know your actions have been appreciated:
All right, children. It's time for Three Dog to be honest with ya. Here it is, plain as day - I used to think we were all well and truly fucked. The good ole U.S. of A... ahhh, she's a mess. I had pretty much written us all off. But that was before a certain kid from Vault 101... I've always given it to you straight, have I not? For good or ill, Galaxy News Radio has been the voice of truth on these airwaves. So believe me when I tell you that I was wrong. Dead wrong. That kid from Vault 101 is the Last, Best Hope of Humanity. We'll get through this, children. You just gotta believe. For now, listen close, as I share yet another of our friend's adventures.
In an earlier example, right after meeting James' child, he ends his radio message with a plea to James to let his son/daughter know how they are doing, because their child misses them.
Finishing the violin quest for Fallout 3 and listening to it on the radio, while looking over the wasteland.
Agatha is a sweet old lady who's managed to use her musical talent and find joy in a Crapsack World. There's nothing about her that isn't heartwarming, and it's a colder bastard than this troper who can give the last violin in the world to anyone but her.
And it was from a Vault that turned the dwellers into mindless killing machines, you were giving hope back to the wasteland, another chance to listen to that sweet music again.
After completing the Reilly's Rangers quest and turning in some map locations, at some point you'll run across Donovan in a fight with some supermutants. He tells you that he tracked you on the Geomapper so he could give you some items. If you ask why, he just smiles and says "Rangers take care of their own."
After hours of hard work and determination the feeling you get from having a good lone wanderer climb atop a cliff or building to survey the capital wasteland. Yeah, raiders still harass travelers, but as settlements grow and flourish they'll slowly be thinned out. Okay, some people are still barely scrapping by just to make it through the day, but you've helped as much as you could, saved countless lives, and made several much better. Yes, the world is still irradiated, full of hostile wildlife, and mostly withered, but thanks to you, Harold, and your dad it has a legitimate chance of recovery. Things might still be pretty bad and it'll never be the same as it was before, but in a couple of centuries or maybe even decades natural life will return to the wasteland. Green trees, clean water, people who can live in safety and comfort... War. War never changes...and neither does humanity.
That was beautiful.
There is one beautiful moment at the end of the main story. Your father was slain, his last attempt to bring life to the wastes was in the iron fist of the Enclave. You fought every last one of them to the man and got justice by your father by slaying his murderer, Colonel Autumn. Now his Project, his one dream, the result of everything he has worked and bled for is filled to the brim with radiation and ready to explode at any second. Selflessly, you dose up on Rad-X and step inside the chamber to stop this horrible nightmare. But wait! He never told you how to do it! He never gave you the code to activate the system! If you don't activate it, everything you worked for will be for naught! Then your father's voice rings in your head. His loving voice speaking to your heart: "'I am Alpha and Omega, the beginning and the end. I will give unto him that is athirst of the fountain of the water of life freely.', Revelations 2:16. It was your mother's favorite passage..." '2-1-6', you type into the keypad and pray that it will work. You press the enter key. As the machine whirs to life and slowly fills the chamber with radiation, you fall on your weakened legs. The room slowly goes dark. "Thank you...Dad."
Two weeks later, you wake up and realize wake up and look around, seeing Elder Lyons has been keeping tabs on your status, as well as any followers you may or may not have had. You just found that you hadn't died and can't find peace in the afterlife as you thought you were going to. You ask Elder Lyons what happened and he explains everything that's been happening. You realize that you didn't die because it wasn't your time to die just yet. Some unearthly, all-knowing entity decided you needed to live because the Wasteland still needs you. So you get up and decide to continue to fight the Enclave until every last one of those bastards is dead.
A minor example: Have good karma and have Fawkes, a Super Mutant, follow you. He'll remark that people are very trusting to let you take him with you. He's right. Because of your good karma, they know you will not hurt them and trust that you'll protect them if Fawkes suddenly snaps.
One that's also pretty funny as well as heartwarming: immediately after the Ant-Agonizor/Mechanist Quest in Caterbury Commons (if you convince one or both of them to give up peacefully), put on their costume before leaving town. A kid, apparently a fan of the AntAgonizer or Mechanist, will pop out of nowhere and ask for your autograph. The kid's sheer excitement is hilarious, and it's really sweet that even in the Wasteland, at least one of its young residents can still have an idol, and just be a kid. You can even give the kid the costume!
What's even more special? You really are a hero like the kid thinks you are; you just fight different battles and don't wear an obvious superhero costume.