We have all of the Talisman expansion sets and play with all of them every game. As there are 483 Adventure Cards, 116 Spell Cards, and 13 other types of cards (not counting what will be coming out with The City), this leads to having 1,170 cards in play each game. That's a lot of cards to organize, and very quickly stacks of cards become unmanageable. This can help.
My wife went through and made a simple cardboard holder for each set of cards (Adventure, Spell, Highlands, Dungeon, each Draconic Lord, etc.). She simply used an empty cereal box to do this. The sides of each holder go about 3/4 of the way up the card. We draw from the front and discard at the back.
ON TOP OF THAT
For The Highlands and The Dungeon expansions, since the Relic and Treasure cards are very low in number, instead of giving them their own box she simply attached a little cardboard sleeve on the side of the boxes that hold the associated decks. So all of The Highlands cards are in one holder, yet still separated; and all of The Dungeon cards are in a similarly compartmentalized holder.
ON TOP OF THAT
In one holder she placed the Warlock Quest cards, the Quest Reward cards, and the four Talisman cards. On one side of the holder are the Quest cards. On the other side of the holder are the Reward cards. So when you complete your Quest, you discard it on one side and just turn the holder around and draw your reward. But in the middle--with thick separators in between--are the Talisman cards, so that if you want a Talisman as your reward it's right there, no need to search.
She used a similar construction for the Purchase, Stables, and Alignment cards. On one side of the holder is the Purchase deck. On the other side of the holder is the Stables deck. This keeps all of the items that can be purchased in one location. And since there was really no other good place to put them, she put the Alignment cards in the midle with thick separators like that of the Quest/Quest Rewards holder.
This makes in-game organization and storage organization very simple. Clean-up is a breeze as we just have to pick up each box of cards and pack it away.
BUT WAIT. THERE'S MORE.
For the various markers (strength/craft/life/fate/gold) she took one of the little expansion boxes and (once again, using a cereal box) divided the inside into eight compartments. There are four large compartments along one long side and four small comparments along the other long side. In the small compartments we store the large strength, craft, and life markers, and the gold. In the large compartments we store the small strength, craft, and life markers, and the fate tokens. At the end of the game everything gets put away into its proper space, after which we just put the lid back on the box and pack it away. This makes getting the markers during the game much easier as well.
I'm sure others have come up with similar and different ways of keeping everything neat and tidy. You simply have to with this much stuff. But if you're in need of ideas or are looking for better ways, give these a try. They work very well.