First of all, hats off to you for attempting a Discworld RP, it can be a lot of fun with the right people (Discworld fans are probably the ideal players). With Sir Terry's passing earlier this year, it's a great way to keep some of Discworlds concepts fresh in your mind

I always thought that the best Discowrld stories involved elements of our own world reflected / parodied in a way that turns it up until the knob drops off. If you want to do an original adventure this could be a good way to go - otherwise you may end up with a standard fantasy adventure with a Discworld setting (which is fine if that's what you want).

Is there a RL concept or institution that you and your gaming group are interested in that hasn't appeared on the disc yet? If so, it could be fair game for your adventure. Sounds to me like you are already very familiar with major Discworld institutions, so you could hazard a guess as to the effect of such concepts in world and plan accordingly.

Okay, so going back to the OP - I would probably aim to be one of the main guilds professions - thieves, assassin, wizards etc. Although, it might be fun to play one of the more subtly effective professions - Beggars guild, wannabe Barbarian adventurer, watchman or alchemist.

Humans, gnomes and dwarves are fairly well known in DW, but are you allowing players to be vampires, werewolves, zombies? How about goblin / orc? So many possibilities...