I liked that roleplay idea, but killing everyone, is not my style.
Take a different karma route-Done all of em' except I can't be evil... I made an account which I beat the game with once, He was evil, but his dad gave him the "be a better person" speech and it made me feel bad...he turned good after dad died.
Focus on different Skills- meh..
Become the ultimate unarmed fighter (Deathclaw Gauntlet is helpful): I think that unarmed is useless.
Blow up Megaton/Don't blow up Megaton: tried both, the megaton explosion is nice to watch, especially at night.
Pick Perks you wouldn't normally: meh..
Try to complete the main quest as quickly as possible: I always do this.
When I started looking for ways to make playing on the 360 more fun I did things like this:
RPing was very important for me. I always get very bored of a character that doesn't have a good story.
I ignored the MQ a lot. I still do. I would only go as far as getting the Enclave out and about so I could fight with them. I also avoid doing every DLC every time.
I stopped repairing my stuff to 100%. I stopped putting points into repair all the way up to 100 and used the traders more often and didn't invest in all of them and used Moira a lot more.
I have used EW and only used Laser Pistols, although I did use the uniques, and I didn't use VATS. I carried A3-21's PR for emergencies (when I might die) and then I used Unarmed for back up and would use it against Reavers (Unarmed is very much NOT useless).
I limited myself to a rifle, a pistol and a handful of grenades and, when I wasn't playing an Unarmed character I would limit stimpaks carried and also carried limited amounts of weight and items in general. I still only carry about 75 pounds around with me out of habit.
I played one character that used zero stimpaks. She was really fun and never touched the MQ at all, but did go out to PL.
That's all I can think of right now. I tried everything I could possibly think of to make the game more fun. I played it pretty much constantly for almost a year on the 360 before I moved to the PC.