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Is it possible to connect to an Arduino 2560 using a RS232 (DB9) connection rather than the regular connection using USB cable?

I am thinking of this connection scheme:

PC -> USB cable -> USB to RS232 Multiplexer -> DB9 Cable -> Adapter board -> Arduino 2560
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Yes, perfectly possible. You need an RS-232 interface chip - the most common and well-known of these is the MAX232. You can get them as breakouts on eBay.

That interfaces between the DB9 and pins 0/1 (or other UART comms pins) on the Arduino.

If you are wanting to program the board through it you will also need to connect (after converting the voltage through the MAX232) the DTR line to RESET through a 100nF capacitor.

... Exactly like you would with a breadboard Arduino.

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