I vastly prefered ME2's item handling better than ME1's inventory system. The main problem I had with ME2 was that it was so limited. That's changing with DLC, but at launch there were 2 main AR's, 2 main SG, 2 main SR, 2 HP, and 2 SMG, plus the "advanced" AR, SG, and SR on the collector ship. That's a limited number of different weapons to choose from, and aside from a very linear and limited upgrade system, there was no weapon customization at all.
Armor customization was a good thing, but even that was more about looks than anything else. I've noticed very limited effect from the various armor pieces, with the exception of the Kuwashii visor (+10% headshot damage) and DLC armors (which didn't let you customize them, until the Kestrel set).
I want to keep ME2's system as a basis, and expand around it. Give us like 4 basic versions of each weapon type, and let us customise each weapon to a certain degree. Let us buy or research mods to improve accuracy, rate of fire, damage, stability at full-auto, etc. Change ammo back from powers (which frankly makes no sense), and let them be mods like in ME1. This way you can take, say the ultra high damage, ultra low accuracy assault rifle, and mod it to be the most damaging thing in the known universe, but with horrible accuracy...or you can mod it to be more accurate, but keep the damage the same (or even reduced), etc. That provides a level of customization that players want, without an unnecessary and unwanted "loot" system like ME1 had.
Also, let us mod armors the same way. Certain armors have base stats, like one is set for added shields, one for added health, one for added power damage, but can be modded to go totally specialist in that one area, or modded for a more "generalist" approach. This way people can pick the armor that they like the best, appearance wise, but still get the performance they want from different armor pieces.
This is my wish list for ME3. Hopefully Bioware does at least some of the above.