Compatibility & Interchangability of KT88, KT100, KT120 and KT150 Tubes in Tube Amplifiers
are the KT88, KT100, KT120 and KT150 Tubes safely interchangable
  generally speaking in a well built tube amplifier?


The KT120 and KT150 are both pentode devices and the KT88 and KT100 are described as beam tetrodes so no, I wouldn't think these can be easily interchanged even though the data sheets have the same "pin-out". Without delving into all the detail (which you of course can do) there may be several technical differences that may or may not make interchangeability easy or difficult. 

On the Non-Equivalence of Beam-Tetrodes vs Pentodes appears to be a very useful site that might give you reasons to interchange those devices: -



The Svetlana data sheet for the KT88 says it's an exact replacement for the KT100 so I guess these can be interchanged freely.


  are there any downsides (from a musical quality point of view) why one
  should NOT want to upgrade to a larger KT tube? In other words is the
  newly desiged KT150 generally a better (sounding/lifespan) tube than
  the KT120 tube?


I can only comment on the data sheets and these, as usual do not state anything about musical quality.


KT120 data sheet
KT150 data sheet