Best game ever! Any suggestions?

Deus Ex or Bioshock. You won't get any party members in either game, but they have RPG elements in them.

Deus Ex flatout has a leveling system, and everytime you level up you can choose where to spend your earned Praxis Points to unlock new cybernetic Augmentations (hacking skills, invisibility, infrared vision, enhanced strength, etc). You also have inventory management akin to RE4. The game can be played with lethal tactics or non-lethal, and you can use stealth as well. It's all up to you. There is also a dialogue system, somewhat similar to Mass Effect. You won't get to use it nearly as often though, but you can persuade people through it just like Mass Effect.

Bioshock doesn't have the leveling system of Deus Ex, but other than that it is pretty similar. In that game you equip plasmids (essentially magic superpowers) such as lightning bolt, telekinesis, or incinerate to use in conjunction with your guns. In addition you can equip many types of tonics that give you innate boosts, such as silencing your footsteps, increasing melee damage, turning invisible when remaining still, etc. There are a large selection of them, so you can make some great combinations of tonics and plasmids to make various "builds". The tougher (and optional) opponents in the game will require you to really dig into your arsenal and pull out all the stops. You'll need to setup traps with your plasmids, the environment, and guns before initiating the fight. Defeating these enemies will reward you with a currency you can use to buy new plasmids and tonics, so it is very worthwhile.

Both games features HEAVY environment exploration. There is a ton of loot/supplies to get everywhere you go. Both games have hacking mini-games, though Deus Ex's is a bit boring. I love Bioshock's though. Bioshock also has one of the most interesting settings I've ever seen in a game. The atmosphere and design of the environs is just incredible. Also has one of the most notorious plot twists in gaming from recent memory. It's a great game. I recommend it over Deus Ex. Not so hot on Bioshock 2 though. Still worthwhile if you really enjoy the first, but it was made by a different team and doesn't quite capture the magic of the first game.

I also love Valkyria Chronicles (in my top 5 games of this generation easily), but it is a strategy RPG so it isn't everyone's cup of tea. It does play quite differently from everything else in the genre though, blending turn-based and real-time combat with freedom of movement for your troops, unlike many other strategy games that play out on grids.

And finally, if you want more stuff from Bioware, Dragon Age:Origins is really just Mass Effect but with a fantasy setting. Swords, magic, elves, dwarves, dragons. You name it, it's there. Fantastic game with Bioware's usual.... interesting characters, dialogue system, and superb voice acting. Lots and lots of dialogue when talking to your party members, though you yourself are mute. Being a fantasy RPG obviously leads to lots of skills and abilities to play around with and make various builds. Properly training, equipping, and constructing your party will be important. DA2 is very controversial, and by all accounts a terrible game, so I haven't played it yet. I can't recommend Origins enough though.
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~El Psy Congroo~
PSN ID: FatBeezzee