Las Meninas (1656) by Diego Velasquez

What's really impressive about this is that the real focus of the painting is off-painting.

You can see them in the reflection of the mirror. The couple is sitting for a portrait, and the viewer is placed exactly where they are.

The young girl is a close second for being the subject but her presence mostly directs the viewer to the mirror and therefore the real subject.

318 cm × 276 cm, I bet that would be impressive in person. And a lot to be explored in the frame.

Everybody loses it on the semiotic!