There is not one framework but several, some are mainly Smalltalk, some are more javascript wrappers or ported to javascript. I have omitted a lot of other 'Smalltalks in the browsers'. Another language would be LISP, like [9] in which HN itself is build. I'd love to demo some of these sophisticated front- and back-end frameworks, mail morphle at ziggo dot nl.
[7] https://smalltalkzoo.thechm.org
[8] https://en.wikipedia.org/wiki/Dabble_DB (aquihired by Twitter)
Another good option might be Astro[2] which has a lot of similar goals to Marko, but lets you “bring your own framework” for the interactive parts, so you can achieve a similar experience to Marko with more mainstream tools/syntax.
Don't overcomplicate things, simplicity is often underrated on the web side of development. This is coming from a guy who writes low level embedded c and c++ on a daily basis.
It’s also tempting to go jamstack to start a new frontend project. Some of these boilerplates are very bleeding edge however and you will be spending a lot of time learning the convention of each individual boilerplate. I’d be hesitant to start a new jamstack project.
MobX + React + Websockets looks good for some things. (Controller apps for my home IoT system)
For other things where agility really matters (say a system for building machine learning training sets where you might want to add new tasks) I'd ditch the SPA because I wouldn't want to have to modify the front end just to add a new task.
I'm also dreaming about making systems that are WebGL based and not quite sure how I'll do it.
That said, React seems to be hugely popular these days.