yeah, its no problem to fit the 6.5s in the front if you have a rotozip and a drill.
i would go with 5.25 however of a high end component line unless you don't mind paying the little bit of extra money.
also, while you have the rotozip or jigsaw out make sure to also cut thin mdf pieces to seal the two large holes in your front doors- they will make an incredible difference in the way the speakers respond particularly when used in conjunction with sound deadening (sound deaden then attach the thin mdf with sheet metal screws)
i would leave the stock wiring in place until you run more than 50 watts or so, i am going to upgrade my own soon. it is easy on the passenger side, but will be tough on the drivers side because the "connector" thing that you'd think would be hollow and you could run your wires through actually is not like that. i may just drill a new hole in my door.
i personally am in the process of doing all of this and installing 3-way (6.5, 4, and tweeter) components. you need to use kickpanels or do a lot of surgery elsewhere to your truck to run 3-ways, but they will give the best of both worlds and that way you avoid asking this question. btw- i am running mine off of a rockford fosgate 500.2 amplifier so they'll have plenty of power