Any system that prevents from stockpiling is a good one in my eyes: unlimited storage, drop, hide and collect later on, ... That would have me focus on becoming wealthy. Destroying on removal or a system of lose items ... it shifts the problem to intelligent resource management rather than dumb drop-and-retrieve.
I remember when playing The Settlers of Catan, when a 7 was thrown all players that held more than 7 resources were to dismiss half of it. The rule was applied for the same reasons: stockpiling ruins gameplay.
Intelligent resource management can be a great addition to a role-playing game. Generally, I think that the early stages of a game when you can't buy everything are much more interesting than the endgame when you've got loads of money and nothing you really want to spend it on. Becoming the richest person alive might give you the satisfying feeling that you've achieved something in the game, but it can also lead to boredom and frustration: The player might not bother to smash or open containers or to pick up loot anymore as the chances to find something useful are so slim. And selling stuff that you don't need is almost pointless when you already have twenty times more money than the most expensive items would cost.
I think that both inventory space should be limited and traders should only buy limited quantities of any item before prices drop, even to 0. That way, it might rarely make sense to run back and pick up stuff you couldn't carry the first time. And it could easily be explained in-game: "Another orc helmet? Sorry, but I still couldn't sell the last 20 ones you've brought me. I simply don't have any orc customers, and collectors of such trophies are rare. Maybe you'll get a few coppers at the scrapyard, though."
At first, I also found it hard to leave loot behind in The Witcher, but in the end I was glad I didn't run back and forth umpteen times just to make some money I wouldn't have spent anyway. In most RPGs, one ends up with tons of money and very little left that is worth buying. Truly limiting money as a resource and thus making it impossible to buy all of the best items might be the base for some interesting (though hard) choices in the late game. If heroes can't achieve everything, e.g. when they have just two curing potions for three sick people, why should they be able to buy everything?
It's plausible that the number of items characters can carry is based on their strength, but it's also a big advantage for those who consider strength their main attribute anyway, i.e. warrior-types. It would be nice if this was counter-balanced by other stats also having a non-combat use - intelligence could enable certain clever dialogue options, for example.
It would also be plausible to give money a weight. In many games, equipment has a weight that counts towards your carrying capacity, but you can carry limitless amounts of money. A single coin doesn't weigh much, of course, but it adds up. Assuming a gold coin weighs 5-10 g, 200 or 100 coins already weigh 1 kg, and a fortune of 100000 gold (500-1000 kg) could not be carried by anyone. A bank account might be a way out of this, though at a risk - the bank could be robbed, which might even be the start of a quest to get your money back. Collecting valuable gems and jewels could be another alternative: A diamond doesn't weigh much, but can be worth a small fortune in gold. Some traders might not accept gems as payment, however, and a few swindlers might try to sell you fake gems. If you've got some expertise in jewelcrafting/gemcutting, you should be able to see through their sham.
