Especially since removing one hand from the weapon or putting it back is essentially a free action, there is no real issue with using Spellstrike with a two-handed weapon. It would be the same thing as replacing the weapon attack with an Unarmed Strike, which you could even do with the same hand that cast the spell. The Touch attack associated with touch spells is free action anyway. But here is where things get really fun, from the Core Rulebook:
You can touch one friend as a standard action
or up to six friends as a full-round action. Alternatively,
you may make a normal unarmed attack (or an attack with
a natural weapon) while holding a charge. In this case,
you aren’t considered armed and you provoke attacks of
opportunity as normal for the attack. If your unarmed
attack or natural weapon attack normally doesn’t provoke
attacks of opportunity, neither does this attack. If the
attack hits, you deal normal damage for your unarmed
attack or natural weapon and the spell discharges. If the
attack misses, you are still holding the charge.
So spellcasting Monks or characters with Improved Unarmed Strike can substitue an Unarmed Strike for the touch attack normally granted by the spell. With spells that have multiple hits available, like Chill Touch, this can get REALLY nasty. One hit first round, with Flurry of Blows + Spell on the second? Dastardly.