Best starting skills:
-Repair (TOP priority, involved in several quests and imperative towards ALL offensive AND defensive stats)
-Lockpick (get to at least 50 early on, 75 if you hate being denied a fat loot cache here and there)
-Melee/Small Guns (tag a combat skill for good measure - these two are always the most practical)
Best SPECIAL distribution:
-Intelligence (TOP priority, levels you up faster, and with greater skill point rewards)
-Strength (gives you increased carry weight and melee damage, plus access to Strong Back perk)
-Endurance/Agility (both give great, practical benefits to combat and passive abilities)
Personal note: In Fallout 3, I find Charisma to be basically worthless, and Perception almost as bad - their benefits are weak, and easily compensated for or worked around. Luck is great to have, and there are even valid builds centered around high Luck, but the other 4 are simply better.
Best early game perks:
-Educated (TOP priority, get it at Level 4 to maximize skill point gain over time)
-Comprehension (NEXT priority, get it at Level 5 to double the skill point gain of all skill books)
-Intense training (increase your SPECIAL stats when you are underleveled for the perks you really want)
HONORABLE MENTION: Swift Learning (if speedy leveling is you primary goal, dump 3 points into Swift Learner at 2, 3, and 5, and hold off on Comprehension until 6. This might cause you to miss out on perks that actually strengthen your character, such as the benefits of Intense Training, but you will level up extremely quickly and overwhelm enemies with pure skill point advantage.)
Personal note: Maybe every once in a while, it might be worth choosing a perk that simply increases your skill levels; don't do this for any perk that doesn't grant at least 15 skill points or a passive bonus effect (Little Leaguer, Daddy's Boy/Girl, Thief, Scoundrel, Gun Nut are wastes - Tag!, Size Matters, Impartial Mediation, and Silent Running are valid options, but still not ideal, unless you pick up Silent Running for stealth/crit builds).