First debugging results:
When calling format or quality the call functions of ImageMedia are called, but not the __call function:
https://github.com/getgrav/grav/blob/develop/system/src/Grav/Common/Page/Medium/ImageMedium.php#L423
https://github.com/getgrav/grav/blob/develop/system/src/Grav/Common/Page/Medium/ImageMedium.php#L535

__call Only gets called in the derivatives() function via resize:
https://github.com/getgrav/grav/blob/develop/system/src/Grav/Common/Page/Medium/ImageMedium.php#L323

That is the reason why the alternatives are never called via format and quality. It only works for the single image, as it is passed here as parameter:
https://github.com/getgrav/grav/blob/develop/system/src/Grav/Common/Page/Medium/ImageMedium.php#L627

I am not sure how to fix this yet.

Combining cropZoom() or flip() with derivatives() also fails to work. So maybe all functions in combination with derivatives may yield incorrect results.

The results depends on the order of applying flip(), cropZoom() and derivatives().

Flip:
When using, flip.derivatives, only the last is flipped. When using derivatives.flip, all images are flipped.

zoomCrop:
zoomCrop shows a similar result, but adds a sizing issue.

Original: 400x800 (portrait)

{{ image.cropZoom(800, 400).derivatives([100, 200, 300]).html() | raw }}
Only one image, the original, is cropZoomed, the rest are only resized to right proportions.

• 100 -> 100 x 200
• 200 -> 200 x 400
• 300 -> 300 x 600
• original -> 800 x 400        <- cropZoomed

{{ image.derivatives([100, 200, 300]).cropZoom(800, 400).html() | raw }}
All images are cropZoomed, but the sizes are way off:

• 100 -> 3200 x 1600          <- cropZoomed
• 200 -> 1600 x 800            <- cropZoomed
• 300 -> 1066 x 533            <- cropZoomed
• original -> 800 x 400        <- cropZoomed

I really think this whole media handling needs a rewrite as it's a confusing mess in there. Unfortunately, that is probably not going to happen until version 2.0.

So until then, it's not really possible to use srcset in some easy way with manipulated images, right? Any timeline for v2.0?

Being a different discussion and not knowing your use-case...

As a 'photography enthusiast' I would hand craft my images using Photoshop, Gimp or the likes. Then, when satisfied with the result, apply image.derivatives().sizes() to create srcsets as the last stage of the workflow.

That's a great advice and most likely will have to do this. It's just that these images are already crafted in Ps to be published :) They only wouldn't fit the layout of a webpage. But it seems will have to create cropped versions too :)

If crafted images don't fit the layout of the website, they either have not been crafted for the website's layout, or the website isn't designed properly to accommodate the crafted images...