I recently had an interesting experience with an UNO clone that has been working fine for months. The tools display showed a valid port connection, but when I attempted to upload I got a no port found error. After a few more tries the port disappeared from the tools menu.
I tried the usual things - new cable - different port etc - nothing worked. I tried the cable with another board using the same USB-Serial chip. It worked fine. Now I was suspecting that the there was a problem with the USB chip connection.
I got out my DMM and tested the connection between the data pins on the USB connector and the D+ an D- pins on the chip. There was no connection. Next I traced the connections up to the vias that went under the chip. All were fine. I thought I would solder in jumpers from the USB connector to the pins on the chip. Then I thought just reflow the pins on the chip and see what happens. I remelted the solder on the pins and then did a test. There was now connectivity! I connected the board and uploaded the Blink example. It uploaded and ran. Problem solved. Apparently there was a marginal connection that worked for quite a while before failing.
Most of you will not see this problem, but if all the usual things don't work start thinking about more improbable causes. On the other hand if you have a new board that doesn't work out of the box it could be a hardware problem.
Another test you could do if you suspect an onboard USB-Serial problem is to bypass the onboard chip and use a USB-Serial cable. Connect the pins to the board pins (remember to put a 100nf capacitor in the DTR to reset connection path) and see if it works.