You can reference application static files as Cards images. Please note Cards expects ampersand (&) substitution syntax. Usual way of referencing application static files cannot be used. i.e. #APP_IMAGE#myAppImage.png. Also, APP_IMAGES substituion needs to be substituted from the server as it is not one of the built-in substitutions client-side supports to render the value.
Let's say you are using IMAGE_URL column as Cards media image, use the following query to reference the application static file:
select :APP_IMAGES || file_name as image_url
from apex_application_static_files
where file_name = 'myAppImage.png'
and application_id = :APP_ID
You can also define your own CSS classes to customize Cards styles. Float with Custom CSS example displays Cards Icon and Media differently using page inline CSS.