Man, this project really turned into a survey of USB-I2C master chips.
Created revB with a MCP2221A and performance was very disappointing. Had some strange glitches where it would not send the stop pulse for a long time after the byte to be written was sent, for a while I thought it was just sending extra stop pulses they were so far from the transaction. The in-tree kernel driver is supposed to let you use the free gpios as a gpiochip under /sys/class/gpio, and it did enumerate there for me but I couldn't get it to work. Bitrate was also was fixed at 333kHz, which is too fast for the ATECC608 chips to wake up and there was no in-band way to change the baud rate short of a kernel module rebuild (I didn't want to pull in any libusb code to configure it from my code, shouldn't have been too hard but meh, the stop pulse glitches were already too much).
Will switch revC to FT260. Actually got a dev kit for it first this time, and using an out-of-tree driver allows changing the bitrate from userland via a /sys/bus/hid/drivers/ft260 node!!! (The in-tree driver is old and missing features, hopefully they get merged soon). Haven't tested the uart or gpiochip iface but they enumerate now. It also correctly does the 0 byte write to the 0x00 general call address for device wake up. This along with dynamic userland baud rate change is nice, should be able to switch to 100kHz for wake up then to 1MHz mode for lower latency (only tested to 400kHz so far, since that is limit of PCA9544).
FT260 driver:
https://github.com/MichaelZaidman/hid-ft260revB / revC also add 4x TNGTLSS variant chips to the 4x blank ATECC608Bs, total of 8 ICs, and a more compact layout.
FT260 seems like a winner, I'll probably use it on some other test / calibration fixtures we have coming up. I might switch from PCA9544 to PCA9849 for 1MHz fast mode support.