Running macros in game vs via ISBoxer basically amounts to a few basic differences:

1. ISBoxer makes it easier to manage your sets of macros vs in-game (IMO) and allows any keybinding to be assigned to them regardless of whether you're out of on-screen buttons.

2. The in-game macro edits will apply immediately vs having to /console reloadui to get the ISBoxer export to apply if you update it while playing.

3. ISBoxer lets you build a single macro that will conditionally include bits based on whether a character matches a name, a slot, or any arbitrary grouping (see: Action Target Groups)

4. ISBoxer macros can exceed the max character limits without needing an explicit addon to enable that. (At least, I think this still applies.)

5. ISBoxer macros can target e.g. {SLOT1} which gets replaced dynamically with that character set's slot 1 character name, meaning you don't have to manually go change everyone's macros when you rearrange the group or create a new group of characters.

I'm sure there are more. I find the ISBoxer include conditionals very powerful and I'm probably not using even half of its capabilities. As an example, this is the first of 6 "Combat" step macros I use in my primary DPS multi-step mapped key.

Code:
#showtooltip
/stopmacro [flying][noharm][channeling]

!if (character in "Monk" and character in "Tank") /castsequence [nochanneling] reset=combat Keg Smash, Keg Smash, Expel Harm
!if (character in "Monk" and character in "DPS") /castsequence [nochanneling] reset=15 Expel Harm, Tiger Palm, null
!if (character in "Monk" and character in "Healer") /castsequence [@targettarget][@{SLOT1}][] reset=15 renewing mist, null

!if (character in "Hunter") /cast [nopet][@pet,dead] revive pet
#!if (character in "Hunter") /castsequence [@pet,help,exists] reset=8/target misdirection, null
!if (character in "Hunter") /cast [harm] dire beast

#!if (character in "DruidCaster") /castsequence [harm] reset=20/target moonfire, null
!if (character in "DruidCaster") /castsequence [harm] reset=combat/20 starfire, moonfire, starfire, Force of Nature, starsurge, starfire, moonfire, starfire, starfire, starfire, starfire, starfire, starfire, starfire, starfire

!if (character in "PaladinProt") /cast Hammer of Wrath

!if (character in "Warlock") /cast [@pet,dead] summon felguard; [nopet] summon felguard
!if (character in "Mage") /cast [@pet,dead] summon water elemental; [nopet] summon elemental

!if (character in "Warlock") /castsequence [harm] reset=15/target corruption, shadow bolt, drain life, life tap, soul fire, shadow bolt, drain life, soul fire
#!if (character in "Mage") /castsequence [harm] reset=10 frostbolt, ice lance, frostbolt, frostbolt, ice lance, frostfire bolt
!if (character in "Mage") /castsequence reset=5 Arcane Blast,Arcane Blast,Arcane Blast,Arcane Blast,Arcane Barrage

!if (character in "Priest") /castsequence [spec:1] reset=15/target shadow word: pain, archangel, power word: solace, archangel
#!if (character in "Priest") /castsequence [spec:2] reset=15/target shadow word: pain, vampiric touch, mind blast, mind flay, mind flay, mind flay, mind blast, mind flay, mind flay



/startattack
#/script UIErrorsFrame:Clear()
Result for Monk team slot 5 "Combat1" macro:
Code:
#showtooltip
/stopmacro [flying][noharm][channeling]
/castsequence [nochanneling] reset=combat Keg Smash, Keg Smash, Expel Harm
/castsequence [@targettarget][@Fantazma][] reset=15 renewing mist, null
#!if (character in "Hunter") /castsequence [@pet,help,exists] reset=8/target misdirection, null
#!if (character in "DruidCaster") /castsequence [harm] reset=20/target moonfire, null
#!if (character in "Mage") /castsequence [harm] reset=10 frostbolt, ice lance, frostbolt, frostbolt, ice lance, frostfire bolt
#!if (character in "Priest") /castsequence [spec:2] reset=15/target shadow word: pain, vampiric touch, mind blast, mind flay, mind flay, mind flay, mind blast, mind flay, mind flay
/startattack
#/script UIErrorsFrame:Clear()
(Yeah, I comment stuff out and leave it in there. It's perhaps inelegant, but it works.)

It's a pretty slick tool. Once you start using the features, you realize how much work you save when you create new characters/classes/groups.