I played fallout 3 through only once and did like every quest there is and never did a second play through because I just didn't want to leave my character. Same thing with fnv. I know I can just load a save and go back to but I also want to see some other sides of the game.

I want to hear what route you chose and how fun it was. And if you played more than 1 I wanna hear your suggestions on which one.

I would like to know whether you did side quest before you did the main ones. And if you played good or bad. Thanks guys

You can change the faction you sided with. That's 4 different playthroughs right there.
You can change your combat style. Makes huge difference.
You can also set your own rules. For instance, check out the http://www.gamesas.com/index.php?/topic/1205789-the-dead-is-dead-thread-3/. Lots of good roleplay material there.

For a second playthrough, change factions and how you kill people.

I would suggest explosives or Hand to Hand. Both are fun.

In my first 7 games, I didn't always take the game to the ending battle. I still have those saves and can do it anytime but once I'd done it, it wasn't the point anymore for me. My favorite part has been building each character from Doc Mitchell's house on up. I learned to mod and have the Unlimited Companions mod so I can have more than two with me. My favorites to travel with have been Boone, ED-E and Arcade. That's a sniper, and two EW companions. I tend to use EW but I'm not a great shot so often just use the 12.7 pistol or 12.7 smg. That's one thing I change up. A couple others have been: One character, Pipi, had INT1 and that was my personal "hardcoe" game because you don't get that many points when you level up and a few other things are a challenge. Dawn was all Unarmed and I had never done that before. It was a blast to knock out a Deathclaw with Pushy. It was scary but fun. Those are a few suggestions.

One thing I did (and for Fallout 3 as well) was switch genders on my 2nd playthrough. I was surprised (I'm a guy) how much fun building and playing a female character was. It was also interesting, because being a female I enjoyed being more sarcastic in conversation (like my wife). ha ha.

Also, just by taking a different route the second time made a lot of things different. I went straight north (using stealthboys to get safely past the deathclaws) and made my way all the way up to Jacobstown.....where now we will start the game as far as quests go.