Major or minor, doesn't matter. Just something you've been hoping for to happen for years and years, despite many promises and declarations made of that thing happening. Only for it to never happen at all.
Two things come of mind to me.
For America, we will never ever see an Independent take hold of the presidency. It hasn't happened for over 170+ years and that's a long damn time since the last time a person representing an independent party has ever held office. The only successes an independent party ever sees is smaller governments or some seats somewhere in the house or senate, that's about it.
But every election cycle, people are hamming up about how it's going to be the year for independents, until the primaries come and go and we're back to falling on two parties. I've stopped getting my hopes up and I stopped hoping the moment Bernie Sanders, who originally did run as an independent for the presidential election in 2016, had to turn to running as a democrat because even he realized that was the only way he was going to get votes at all.
One other thing and it's gaming related is that, there are still Nintendo fans out there hoping for a Mother 3 english release. It's a game that was released in 2006 and it never left Japan since. Despite all of the re-releases of Mother and Earthbound, Mother 3 has not gotten a localization. It's been released as a fan translation and I feel that's the best we're ever going to get.
It's been 18 years since it's original release and I think there's no point in hoping now for Nintendo to release it. They're too busy suing people.
gestures broadly at all things
Humanity in general. People are jerks. Maybe Agent Smith was right all along.
Other than that... Half-Life 3 ever being made.
The bullies have won. Biff Tannen is about to get elected again, and there is hardly any empathy left.