In any case, it was my understanding that the main engineering difficulty with the Defiant was that it's power profile was RIDICULOUSLY overpowered for it's weight class, which implied the early prototype that Sisko had was essentially a flying bomb, which could barely keep itself from bleeding through the cloaking device, even when doing silent running.
One has to give Chief O'Brian credit where it's due, though, for managing to make it work and, apparently, improving and stabilizing the design, which no doubt encouraged more of the things to be built.
Overall, this seems to come down to a couple of points.
-Construction difficulties- Not much of a surprise, given how much power is being crammed into such a small form factor. I don't have the relevant specs, but I imagine the Defiant is small enough to (barely) fit in the Enterprise's main shuttlebay, and yet, the two ships are probably comparable in terms of tactical power. It's really no surprise the Defiant has unique construction difficulties--It's the only starship I've noticed that has explicit (and effective) ablative shielding, for example, which I imagine can't possibly be easy to manage, given the kind of things one would need to defend against in the even of a deflector shield failure (exotic energies, antimatter, etc). In fact, I might even go so far as to say that the ablative shielding may be the limiting factor, forcing both the small size and the limited run, given that, if it WASN'T made of exotic materials, then it would be a standard starship feature and not something exclusive to a tiny warship class.
-Related to the first point, it may be possible that Starfleet desires to keep the production run of the Defiant limited in order to keep it cutting edge. I'm not sure I've ever seen one of this ships with an NCC designation, if I'm not mistaken, they've all been NX models so far. That may be an indication that they want to the Defiant to always be 'experimental' in that it's always going to have the latest offensive and defensive gear and that new models are always going to have the fanciest designs. As such, the class may never 'stabilize' and will always be a testbed model, which isn't the worst idea from a cold equation standpoint, since, if the worst should happen, the Defiant only has a crew of a couple of dozen, as opposed to a full on starship with a crew of hundreds...
-Design philosophy- The Defiant is a single purpose ship, which Starfleet seems to have some resistance to, preferring their starships to be at least somewhat modular and adept at nearly any task put to it. While the Defiant is certainly great at tactical tasks, and possibly a bit of surveillance here and here, that's about it. I would certainly hesitate to assign it for many peacetime exploration/tasks, as it's design and philosophy would send entirely the wrong message to other races, diplomatically speaking. Especially as compared to classes like the Galaxy, which, while heavily armed, were obviously primarily designed for a more peaceful purpose, even if said purpose was eventually shown to be a bit too naive, given the events of later seasons of TNG and DS9 (namely, the Borg and the Dominion).
So while I'm sure the Defiant class is certainly something that Starfleet won't allow to lie fallow, I'm also not sure we'll ever see it in large numbers, but I'm more than willing to be wrong, as I'm just speculating...