First off, I love it when devs look to the community that supports them for their ideas. Thanks for giving us a chance at some input!
I definitely feel the need to echo others in this thread in relation to Titan Quest's skill system. It's easily my favorite system thus far, with the possibility for multiple character builds in each mastery, and even more when mixing them together. I'm certainly not advising you copy it, but I do believe some time trying it out and experimenting with builds in that game might give you some ideas for yours.
Unique items. I know they're normally in these sorts of games but I feel they ought to be more... well, unique. Angband has some of my favorite uniques. They'll usually be better than other items of their type in the typical ways, but then have effects like double or triple damage against certain enemy types, the ability to cast spells with a cooldown, special immunities not normally granted by any other items and fancy abilities like being able to see enemies through walls. Oftentimes they'll also have minor downsides, which i feel really helps balance them out. "I like this bonus regeneration, but do I want enemies to notice me half a screen sooner than usual?"
Another source of fantastic item design is King's Bounty. Artifacts have Keepers the player needs to defeat to improve the item to its next level. This gives some incentive to pick a favorite artifact and lug it with you throughout the game, eventually upgrading it when you feel you're strong enough to take on its Keepers. Another way of improving certain items is to perform actions the item likes. An Elven bow might be improved by having elves in your party, and by killing orcs. A dwarven axe, on the other hand, might become weaker because you've just used it to kill some dwarves.
Hm. Seems I've rambled on with what other games have done already... well, anyways, those are some item related elements in other RPGs I've truly admired recently. Maybe they can offer you some inspiration as well.