Is it possible to swap out a 48 MCU for one with 64 pins?
You can deal with unused pins by leaving them open and setting them to output mode (if possible) or by tying them to GND or Vdd, preferably through individual resistors. 

Typically they will float for a brief interval during power-up while RESET is asserted then assume the output mode. Usually that's not a problem but in some cases it may thought to violate 'best practices' or there may be some consequence of having a brief period where power consumption is increased, or perhaps RESET can be asserted for more than a brief period. In those cases, you can set the unused pins as inputs (typically the default) and use pull up or pull down resistors. 

The reason for using individual resistors is that if the input were to become an output inadvertently (due to a hardware glitch or firmware error) then the output could be shorted. 

You may have to do some thinking before redoing the PCB layout- most MCUs have pins that are reserved for certain purposes, and they may be shared with other similarly reserved pins with or without some kind of re-mapping ability.