Can you afford 500 ATtiny85s?
If you can limit the overall throughput to around 100kbps (or whatever the USB is capable of) I think you can do it with one master and 500 ATtiny85s.
There is an 85 per sensor. Each 85 does nothing but read the ADCs (8 bits for now) for it's sensors and get interrupted by a pulse from the master (the pulse is common to all 85s). In receiving this interrupt the 85 places the last valid reading into the USI register.
All 85s are daisy chained MOSI-> MISO etc with the chain starting and ending at the master.
The master does nothing but pulse the 85 interrupt signal, then do 500 SPI transfers. The data goes into a circular buffer to be read by another process that spits it out the USB.
This should be doable for 16-bits and maybe 2-3 sensors per 85 to reduce the hardware.
The clock and interrupt lines would need some serious buffering.
This has no overhead for mapping sensor ID to data and just a few tight routines that shift data.
Well you did ask for ideas