While Fallout and Fallout 2 feature turn-based combat and top-down isometric view in a 2-D engine, Fallout 3 features real-time combat and first o third person view in a 3-D engine. Fallout Tactics and the canceled camioneta, van Buren featured both turn-based and real-time combat and a top-down view.
Perks and Traits have been merged. In Fallout and Fallout 2, Traits were chosen at character creation, and were commonly a combination of a powerful advantage and a potent disadvantage, where Perks were purely advantageous.
In the SPECIAL character system, the number of skills has been reduced from 18 to 13, traits have been removed and perks are selected every level instead of every 3 to 4 levels.

Not actually a fat man, which would in its own way be hilarious, the Fat Man is a "shoulder-mounted tactical nuclear catapult." In layman's terms, that means it's a hand held weapon that basically shoots nuclear bombs at people. It should certainly incinerate your target, but do be warned, there's a high possibility it will also incinerate everything around it (including your mates and possibly yourself), as well as leaving residual radiation.

The name comes from the segundo atomic bomb that was dropped on japón in 1945. Unsurprisingly, in the game's Japanese release, this had to be changed, with the Fat Man becoming the Nuka Launcher in the Land of the Rising Sun. In Japan, the side quest whereby tu can choose to detonate the atomic bomb in the town of Megaton was also removed from the game.