Annoyed at the frequent comparisons between Bethesda Game Studios' Fallout 3 and Gearbox Software's Borderlands, WarpZoned's Nicole Kline penned an editorial in which she points out the differences between the two post-apocalyptic titles. Here's a sampling:
There are few overlapping similarities about the gameplay. Borderlands a first-person shooting role-playing game is all about shooting up your enemies, finishing quests, and looting, looting, looting. In Fallout 3 a third-person shooting role-playing game it's all about figuring out the best ways to defeat enemies, be it with a gun or a melee weapon or stealthing around them and avoiding battle completely. It also includes a lot of quests, and you can loot, but not in the same Diablo II style of Borderlands.
The skill systems are totally different in both games as well. In Borderlands, you get skill points that you can then assign to different aspects of your character's offense or defense, primarily to weapons, armor, shields, and your special moves. In Fallout 3, the skill points are far more complicated you can assign them to things like thievery, bomb making, weapon creation, and a ton of other options. The amount of detail that goes into the skills is a reflection of the intense amount of choices you have for each situation you end up in. Fallout 3 is a far more complex game than Borderlands; in Fallout 3, you can create your own weapons, break into buildings, and customize just about everything, while in Borderlands, you use the weapons you find, and follow a basically linear path everywhere without any complicated choices along the way.