Both are in my Top 5 bands. They have both yet to release a bad album, and if they stay gone, Isis never will.
Comparing them is a difficult task though. They have similar traits in that they make albums rather than songs, songs can be very lengthy and their fans of one band will probably like the other (if they get to hear them).
The approach the bands take in making songs is completely different though. Opeth usually go for long, complex, pacey songs with lots of quick tempo and mood changes. They mix it up by recording quieter acoustic tracks too, but it isn't typical for them to have long interludes in their heavier songs. Usually they only last for 30-40 seconds and they move back. The instrumentation is a lot more direct (for want of a better description) than most Isis work. Guitar riffs and solos take centre-stage when played, whereas Isis layer their riffs and add keyboards, heavy bass, etc.
Isis songs tend to be a lot more "out there". They can start off heavy and then fade away for minutes on end. Few of their songs could be called fast, unlike Opeth. I appreciate that I sound like a complete fanboy douche when I say that their songs "evolve" over time. They kind of float from stage to stage, directed by the brilliant Aaron Harris and Jeff Caxide. Opeth jump from place to place in a much more prog-like way.
I can't make a decision. They're both brilliant in different ways.