From Diablo Wiki
Randomization is used for most Diablo game maps to create a different experience every time a player creates a game. This is one of the main features of Diablo, and permeates almost all levels of gameplay. Maps, items, monsters (at least placement, type and amount) are some of the random elements in the game.
One of the main reasons Diablo I garnered so much critical and cult success was due to the fact that the random elements in the game compelled the player to continue playing, rather than just finishing the game and move on to another. This is a concept known as "replayability" in the gaming realm, and Diablo had much more of it than any other game of its time, from the perspective of many fans.
All Diablo games so far have also had elements of static gameplay, such as unique items as well as parts of the maps always having the same layout (or in some cases, very similar). The Diablo II is a prime example of this.
 Diablo III
Diablo III will have more static elements than Diablo I and Diablo II, in that above-ground areas will all be static, to give a deeper feeling of immersion in the game world. However, although Diablo III contains more static elements in terms of map layout, it could be argued that it is the most random out of the entire franchise.
 Events and Adventures
Events and Adventures are new to the Diablo series with the introduction of Diablo III. Whether a map is static or random, every map that can contain combat will also contain both of these random elements. Events are much more sparse than adventures by virtue of their function, but both appear, and both have a random chance of occurring in a given map. More about Events and Adventures in the randomness section below.
Staying true to tradition, Diablo III offers a healthy dose of randomness on items, including their drop rate, their modifiers, their quality level, and also their ranges of statistics. The generation of items is similar to the system that was seen in Diablo II, for fans that are familiar with that.
In addition to random generation of items, Diablo III also introduces a new version of crafting differing from the Horadric Cube recipes in Diablo II: the artisans. The blacksmith,when provided with sufficient materials, can craft an item for the player. Each item has at least one fixed statistic, but it also has a certain amount of random modifiers that can be attached to the item. Both the fixed modifier and the random modifiers each have a range that can spawn, as shown in the graphic to the left.
 Map Generation and Size
Diablo III has a bit of a departure from previous games in the series as it pertains both to maps and how they are generated, in addition to their possible size. To have a discussion about maps in D3 necessitates a definition: the map tile. A map tile (seen to the right) is one section within a map. In Diablo III, tiles are generally represented as rooms in a dungeon, or various-shaped masses of land. Each tile is fixed in size and shape, but can contain other elements within them. A map consists of inter-connected tiles that form the entire dungeon, and each tile is placed in a random fashion, which is why every dungeon is different from the last from a perspective of structure alone.
Seen below is a picture showing every possible tile in a dungeon from Act II of Diablo III. A tile will be randomly chosen by the map generator within the program, and attached to other tiles, which forms the overall structure of the dungeon.
There is an ever-present concern from many fans that the size and small amount of map tiles will lead to dungeons, while being random, having a feeling of "sameness". However, the design of such a style of map generation is to prevent labrynthine structures as was seen in the Maggot Lair of Diablo II, which always consisted of a confusing maze of tunnels that often lead to dead ends, holding, more often than not, nothing of interest to the player.
While nobody can be assuaged by even the best logic when it comes to maps, due to the fact that a "feeling" of randomness can be very subjective, the maps are indeed random in not only tile selection but size, which was not often the case in the previous two games of the series. In Diablo I and II, the maps were, while randomly generated with much smaller tiles, generally the same size (and usually quite large). In Diablo III, a map that is randomly generated has a much wider range of overall size, as shown in the graphic below.
 Static Maps
The outdoor, or "overworld" maps, are not the only maps that are static. Some plot-heavy maps inside of dungeons are also static (as they may feature scripted events and in-game cinematics), but they each contain their own random bits and pieces. In a sense, there is only one true "tile" to the static dungeon map, but what lies within that tile can differ. Below is a picture showing the third level of the Cathedral (which features Kormac's recruitment quest), and while it isn't easy to display the random nature from a screenshot of a map, certain structures can change in addition to placement of Waypoints, shrines, and other features.
 Randomness Within the Random
While the random nature of items is rather self-evident, there are things to note about the random nature of maps, continuing on from the previous section about events and adventures. An event has its own tile on a map, whereas an adventure generally does not. However, both can be randomly placed with a generated map, with adventures being much more numerous and prominent because they don't necessarily require a map tile.
To the left is a picture showing the Fields of Misery, the blue areas representing areas in the static map that can have random tiles placed within, mostly being events or simply landscape that will change from game to game. A simple way to think about this is that the static outdoor zone is a jigsaw puzzle, and certain areas of the puzzle have their pieces removed. The program, assembling the jigsaw puzzle, has multiple pieces that can fit within the blank areas, each puzzle piece being an event. Adventures, generally not requiring a tile, can occur on any tile in a dungeon, and in static outdoor areas as well. Adventures can be a soldier crawling towards the player, bemoaning their ill fate before becoming a zombie, or an adventure can be a trap that's sprung by interacting with an object.
In addition to this, certain event tiles can contain separate, distinctly different instances of an event. In the Fields of Misery, a farm event can spawn that will have a farmer tasking the player to remove monsters that have inhabited the area, slaughtering his family. In another spawn of the same farm, the farmer may already be dead, and the cellar that was boarded up in the previous spawn is now a dungeon the player can enter in order to purge the house of evil.
 Monsters and Destructibles
Monsters and destructibles function in a very similar fashion to previous entries into the series. Monsters will spawn in random groups and amounts; they will spawn as champions, rares, normal monsters, elite monsters, and their composition will vary from game to game. The constriction on monster generation is that only certain types of monsters are supported by any given map. So, as an example, only gargantuans, zombies, and fallen will spawn within the Den of Evil, but their numbers and composition will be randomly generated. The same holds true for destructible objects within the game, like the famous barrels, jars of ash, or other objects that can be demolished by the player for loot.
The extent of the random nature of the game has yet to truly be seen, as most of the data that was used for this entry comes from the Diablo III beta client and its game files. When the full game is released, the true nature of the random elements in the game will be fully revealed.