Which is the preferred way to go? Will a 4 man rotation tire before the end of the season? 

It all depends on STA and DUR of you SP's..  I usually go with 5 man rotations, 180-200IP SP's are easier to find.. 

I typically run a 4-man rotation, but most owners use a 5-man rotation. I personally believe that you can best maximize the usage of your pitchers in a 4-man rotation. However, it requires more work, as you will occasionally need to juggle your rotation to manage SP and/or bullpen fatigue. Running a 4-man rotation also means you need more innings out of your bullpen, obviously, so you have to set it up accordingly.

Anything from 2-6 works. Just depends on the pitch counts you assign them and whether or not they can handle it.

Hi conspirator-

I've been running a 4-man rotation for several seasons now.  You're welcome to check out the example:

 Hardball Dynasty – Fantasy Baseball Sim Games - El Paso Group W Bench Franchise Profile

I used to have a stable of guys with high STA (90+) and DUR of 30-32, which made for SPs that could pitch 270+ innings.  1 guy nearly cracked 300.  Lately I've switched to guys with DUR about 30, but their STA is typically in the 70s. They almost never pitch complete games, but they regularly make their quality starts.  

The guy I'll call some attention to is Jumbo Martin, the least durable of the current bunch:

 Hardball Dynasty – Fantasy Baseball Sim Games - Player Profile: Jumbo Martin

DUR 27, STA 78.  I've been surprised that he works in a 4-man rotation, but he does.  It's probably worth considering that the relationship between DUR and recovering fatigue/stamina is not linear- it's more like a bell curve.  There's a big difference in rate of recovery between DUR 19 and DUR 26, a smaller difference between DUR 27 and DUR 30, and not much difference between DUR 31 and DUR 34.  So while Martin looks like he should recover much slower than the DUR 31, 33 and 34 guys, those points above 27 aren't as important as the points below 27, so the difference in actual recover rates isn't as big. 

(I don't know if 27 is a specific threshold or anything— it's just the # that's relevant to this example.)

Hope this helps- good luck.