Probably asymptotically we are approaching the regime where we are only making incrementally small discoveries, but the reality is that there is a huge amount that we still do not know, so I am optimistic that new, big discoveries are out there.
I can't go into the details, but we have discovered a new behavior in a material in my little, tiny corner of the world that no one else has seen before. So...something completely new. Also, we are working on an experiment here at work to find evidence of dark matter. Hopefully this is accessible:
https://www.ornl.gov/news/physicists-confront-neutron-lifetime-puzzle
or, a brief discussion about how people were freaking out by the above experiment:
https://www.youtube.com/watch?v=TfMP5BUdKpA
We do stuff every day here at work that has the potential to be the next big thing. So, yeah, I think the next big thing is still out there...