My personal recommendation, as both a player and a developer, is to pay very close attention to how your game will feel to your audience. Make sure you have at least a passing familiarity with probability theory, then make sure your randomization is designed in a way that is more exciting than frustrating.
Some general thoughts:
- As a rule, players should feel excited and happy when they are lucky and content when they are unlucky, not frustrated and miserable when they are unlucky and content when they are lucky. If you are punishing players for something that isn't their fault, your game won't be very fun.
- Be aware of players who might be tempted to try to collect everything. The only options I'm aware of to address this are to either make collecting overtly impossible (such as with a very limited number of inventory slots), to be very careful with drop rates to make collecting reasonable (a firm grasp of probabilistic math is important here. If you don't have one, assume it's much harder to find items than you think), or to just accept that any players who enjoy collection will find your game frustrating, and make it clear that they aren't in the target audience.
- Consider implementing a crafting system, extra uses for money, or some other system to make vendor trash and duplicate equipment more engaging and useful.
- Consider including a few rare but plausible randomized loot combinations which are completely overpowered for the area they are lootable in, but without making them so good as to make the loot of later areas useless and/or uninteresting. For example, a super-low accuracy life-draining sword and a set of accuracy-boosting armour and accessories with poor defense. Each item is okay-ish on its own, but together they become insanely powerful, at least until the sword's attack power begins to lag behind newer options.
- Note that a really good random loot system means a lot of work for you. Players will be expecting a lot of interesting and flavourful gear and items which can be combined in creative ways.
Hope this helps, at least a little. Good luck.
Edit: Oh, another option to appease collectors is to make everything which could be looted purchaseable at a reasonable price later in the game. But this only works if the player knows about it, so make sure it's really hammered home before exposing them to any loot with a potentally problematic drop rate.
Edit II: Other people have mentioned it, but it's worth repeating: It's extremely easy to accidentally make your players feel like there's not enough loot, but it's far less common to hear anyone complain about too much. Especially with random systems, err on the side of generosity.
