I don't see what having a Prestige Class has to do with being in a Guild. Sure, it makes sense that most of the members of the Assassins' Guild have the Assassin PrC, but I'm not quite clear on why this would need to be a strict requirement. I'm afraid there's not enough outside the box thinking going on here. Wouldn't the Assassins' Guild need to have members that can do things other than kill people? I imagine they would have need for administrators, negotiators, possibly potion and magic item makers, etc., not to mention non-killing folks that might be called on to steal stuff, etc.
Perhaps the real problem here is the focus of the group. If your Assassins' Guild is really just like organized labor or something, where everyone in the organization does the same thing (I know, they have administrators too), then that's one thing. But guilds in and of themselves are not inherently homogenous. If you want to make them homogenous in your campaign, then you almost have to force everyone in the guild to join your PrC. If the guild is instead a collection of people that have a common goal, live in a certain area, whatever, then I don't see why you need to make the PrC a requirement.
For example, let's use the Assassins' Guild. If you go the homogenous route, everyone in the organization takes the Assassin PrC. That means that nearly everyone has rogue levels, and probably a bit of fighter or whatnot, but in essence, they are very close to being the same sort of character. This is pretty boring. If you go with the more diverse approach, most (let's say 75%) of the population takes the Assassin PrC - these are the 'rank and file' who go out on jobs. The rest of the guild is made up of specialists - wizards (creating magic items and potions), rogues (stealing stuff, gathering info), bards (lots of possibilities here), fighters (guard duty, protection, enforcers), clerics (healing, creating poisons), etc., who perform functions other than going out on jobs.
I find the diverse approach a lot more palletable. With the homogenous guild, you pigeon-hole every member into a specific class grouping, and most of the characters in your game probably can't join the guild. Maybe that's what you want. But if you really want a good portion (or all) of your characters to join a guild, consider the diverse approach (rank and file with specialists). This better fits a campaign concept of a guild as opposed to a stricly metagaming one.