I've always answered 'Mini Tenth' when I get asked that question, but it's a bit like asking about your favourite band - you like them for different reasons, but often to the same extent. The last 'big name' drain I did that really impressed me was Cunningham Pier. I'm probably a little odd in that every time I've done a top tier drain, I've found it a little underwhelming due to the vast expanse of photos out there - I feel like I've seen it a million times before. I got that feeling when I did GOD for the first time. Take Dwellers' for instance - one of the largest systems in the metro area, with features coming out the wazoo, but it get marks knocked off because it's just so bloody long between interesting bits.
My favourite drains are the little ones that hardly ever get a mention or even a visit, but set your expectations low enough that any features they might have are impressive. Guinea Pigs' Tomb for instance, or many of the Clayton series of drains, are just some of my favourites. It's even better when they're not on a list or have been taken off, but turn out to be nice little detours. Seanile's Tomb is like this, or even the aforementioned Iso's Tomb (which has a cool double grille room in it, but requires too much stoop to be worth it if you don't know what's up ahead).
Then again, there are some drains that I really like because of the memories I have from various visits. Iso's Tomb falls into that category (the first drain I ever found, hence the somewhat unofficial name) as well as a little known drain sometimes referred to as Drongos' Tomb (which has a semi-official name, but it does reveal the location). People who stay on in the Cave Clan often do so because of this social component - it's why for many (but not all) members doing the same old drains all the time never gets boring!