Yeah, you can join all the guilds without any issue. In fact, you can become Archmage while barely knowing a spell... in effect the Fighters and mage's guild quests are both combat based and the Thief and Dark Brotherhood are sneak based... although you can go in sword swinging in the assasination quests.
The minor < major thing comes about because of auto-levelling opposition and effective leveling yourself. In short, you want to get the maximum stat increase every time to you level (you get between +1 and +5 on certain stats each level), so you only want to level with getting +5 in the stats you need. It's complex and tedious, but if you're power-gaming it's the way to go.
The leveling opposition means if you've chosen stats you use all the time, your level will shoot up (as long as you play normally and not metagame) and you'll suddenly find every enemy is a certified bad ass who... especially if you haven't levelled your stats effeciently... on paper should be able to destroy you with ease. Of course, the dodgy AI means that normally doesn't happen, but it makes the game harder.