USB Flash Drive as a main hard drive (Macbook Pro Retina 13" Mid-2014) My hard drive on my mac has died. It became clear as I had the hard drive replaced at a repair shop that the problem is somewhere on the motherboard, thus uneconomical to fix. However, the repair shop tested that a USB drive still works.

As I see it the only option is to get a SDXC hard drive, or a USB 3.0 powered one. The SDXC doesn't support UHS-2, therefore the maximum bandwidth will be around 150MB/s.

As I have researched this I've come to the conclusion that the write/write speeds on high-quality flash drives reach above 300MB/s(for example Sandisk Extreme Pro ), which is comparable to a high quality external SSD, but a lot more portable.

My question is therefore: Is this bandwidth between the hard disk and the CPU  sufficient for the operating system to run smoothly, or is it a completely lost cause?

As I have 16GB of RAM I expect it to work out, am I on the right track or completely lost?

Thank you!
As you have 16GB of RAM your CPU will be mostly playing with it and very rarely access the USB drive, unless you constantly access stored information on the disk.

Common users do not do that.

So I have Firefox, Chrome, Skype, Mail, open and my access to the SSD is minimal. 

see Data read/sec and Data written/sec. 

As I constantly use all of those aps, there is no data exchange with my SSD.

However in your case the OS X engine also resides on the external disk, so I can not tell with certainty.