Those are some inspiring numbers! I have finished all DLC, quests, etc at about 180 hours. My question is how you go back in for another play through when you know where everything is and what is going to happen? Seems like spinning your wheels to me. Help me see the light!
Mods on the PC...
Probably the biggest mod that helped with re-playability is the one that moves the bobbleheads around. Each of the 20-odd bobbleheads gets randomly moved a the start of the game to one of 5 spots. So now, even if you know where all the bobbleheads should be, there's only a 20% chance that you'll actually find them there. I wish someone would do similar for all the skill books, but that's about an order of magnitude more difficult.
Adding Marts Mutant Mod (MM) to the mix also helped for replay.
Turning the XP gain down to 50% of normal means that I need to explore more to level-up, because I can't just do a handful of a quests and get a big level bump.
I try to make each character have a different focus as well. One might be a sniper / sneaky. Another is a mid-range, combat-armor, small automatic weapons type. A third would be a big weapons / heavy armor type. Plus there's the choice of karma, whether you try to stay neutral, evil or good.
But mostly, on repeat playthroughs - I tend to avoid the main quest. Instead, I go exploring and see what I stumble into. The only things I make sure not to do is stumble across an area used in the main quest chains until I'm ready to go there. (Going early either short-cuts the quest chain, or can even break things due to how fragile some of the FO3 quests are.)
I'm level 11 or so on this latest character, and about 20 hours in on gameplay. I still haven't defused the Megaton bomb, and I still haven't gone to GNR or Rivet City. But at level 10-12 is like the sweet spot for me - I feel strong enough to take on most enemies, I have enough ammo to do it, but everything is still a challenge. So this is where I back off the XP gain (with the choose_XP mod) and simply enjoy exploration and doing odd quests. I may even go from 50% XP gain down to 25% or 33% if I feel like I'm leveling up too fast still.