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The details may be of some interest:

The 50GB folder (with fragmented files of various types and sizes) is sitting on a mid-2015 MBP 2.8 GHz i7 with 500GB SSD. The thumb drive is a garden variety of 64GB Lexar™

What settings allow best transfer?
Bluetooth on/off; Wifi on/off; Screen on/off; USB port right/left; etc. Is there anything I should do first to prepare the files for better transfer. For example, I would de-frag a hard drive before a data-transfer in the olden-days when computers were steam powered.

… Or, does it matter since the bottleneck is the USB flash drive?

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Bluetooth, WiFi and your screen have absolutely nothing to do with the transfer speed of USB. Tweaking these settings in the hopes of making USB transfers more efficient is like waxing your car to get better fuel efficiency.

The thumb drive is a garden variety of 64GB Lexar™

Is it a USB 2.0 or 3.0 thumb drive? You can tell if it has a blue tab in the USB connector. That'll be the kicker. If it's a 2.0, the maximum throughput you're going to get is 480Mbps. Going downhill. With a tailwind. On greased skis.

If it's USB 3, you'll get at most 5x the rate of 2.0, but more like only 3x.

As far as defragging your drive, that won't make any difference on an SSD with HFS+ format. Plus PCIe drives run about 24Gb/s or 4x faster than SATA III at 6Gb/s

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