Based on past bad experiences, I try very hard to have my mainline run on straight and smooth track to avoid derailment problems (mainline always takes the straight route on a standard T.O. or the widest on a curved T.O.). I use wyes off the mainline but not on it. I find this especially true if I just want to put a train in motion and not have to worry about it (while tinkering on some other project or portion of the railroad). As always though, you'll have to weigh the pluses and minuses for what matters most to you. One other consideration is if you'll be reversing cars over the wye on a regular basis - if so, give more consideration to using a standard T.O. so cars can be backed up over straight track.
Have fun figuring it out - that's one of the best parts of the hobby in my opinion.