Gestalting is a good way to make an otherwise underpowered NPC more of a challenge, IMHO. Personally I disagree that it should automatically be worth a CR increase, and I don't think it's unfair to treat NPCs differently than PCs, but I think this is a case where player expectations are very important. If your players are going to expect mechanical parity in this area, then they aren't likely to enjoy going up against an NPC that has abilities that aren't available to them, and therefore you're best off not applying Gestalt (or other modifications) to an NPC if you aren't allowing it for PCs. But consider that NPCs already don't have to deal with level adjustment; there is a built-in assumption that since NPCs do not stand in the spotlight the way that PCs do many abilities are much less useful to them.
The biggest consideration is (as often is the case with D&D) actions. A Gestalt Fighter / Cleric isn't any better than a straight Fighter if she never gets to use any of her Clerical abilities. This generally means allowing the NPC enough warning that at least a couple of buff-spells can be cast, and opportunities for healing. But I think you should also consider providing opportunities for the PCs to avoid both of those possibilities. Can they sneak up on the NPC, or delay / kill any minions rushing to warn that the party is about to show up for the final encounter? Can they spot and cut off the bolt-hole that she's planning on using to get out of the line of fire long enough to heal / re-buff and return for round two?
Obviously a lot of this is going to depend on which classes you are planning on Gestalting. If you're going for Fighter / Sorcerer strictly for the extra hit points / Fort save and plan on simply blasting the party with spells, then that's a lot less complicated (and probably calls for a bit of a CR increase).